5-90629546-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032119.4(ADGRV1):c.1839+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,575,870 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0087 ( 22 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 18 hom. )

Consequence

ADGRV1
NM_032119.4 splice_region, intron

Scores

Splicing: ADA: 0.00001590

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.469

Publications

0 publications found

Variant links:

Genes affected

ADGRV1 (HGNC:17416): (adhesion G protein-coupled receptor V1) This gene encodes a member of the G-protein coupled receptor superfamily. The encoded protein contains a 7-transmembrane receptor domain, binds calcium and is expressed in the central nervous system. Mutations in this gene are associated with Usher syndrome 2 and familial febrile seizures. Several alternatively spliced transcripts have been described. [provided by RefSeq, Jul 2008]

ADGRV1 Gene-Disease associations (from GenCC):

Usher syndrome type 2
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Usher syndrome type 2C
Inheritance: AR Classification: STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
febrile seizures, familial, 4
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
nonsyndromic genetic hearing loss
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ADGRV1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 5-90629546-G-A is Benign according to our data. Variant chr5-90629546-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00875 (1332/152236) while in subpopulation AFR AF = 0.0292 (1212/41524). AF 95% confidence interval is 0.0278. There are 22 homozygotes in GnomAd4. There are 634 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 22 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.1839+7G>A		splice_region_variant, intron_variant	Intron 9 of 89	ENST00000405460.9	NP_115495.3	Q8WXG9-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADGRV1	ENST00000405460.9 link	c.1839+7G>A	splice_region_variant, intron_variant	Intron 9 of 89	1	NM_032119.4	ENSP00000384582.2	Q8WXG9-1
ADGRV1	ENST00000640109.1 link	n.1942G>A	non_coding_transcript_exon_variant	Exon 9 of 9	5
ADGRV1	ENST00000504142.2 link	n.605+7G>A	splice_region_variant, intron_variant	Intron 3 of 13	5

Frequencies

GnomAD3 genomes

AF:

0.00874

AC:

1330

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0292

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00570

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00670

GnomAD2 exomes

AF:

0.00258

AC:

595

AN:

230640

AF XY:

0.00204

show subpopulations

Gnomad AFR exome

AF:

0.0303

Gnomad AMR exome

AF:

0.00254

Gnomad ASJ exome

AF:

0.00186

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000321

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00107

AC:

1519

AN:

1423634

Hom.:

Cov.:

AF XY:

0.000932

AC XY:

660

AN XY:

707970

show subpopulations

African (AFR)

AF:

0.0312

AC:

995

AN:

31922

American (AMR)

AF:

0.00273

AC:

112

AN:

41052

Ashkenazi Jewish (ASJ)

AF:

0.00166

AC:

AN:

24754

East Asian (EAS)

AF:

0.00

AC:

AN:

39384

South Asian (SAS)

AF:

0.0000849

AC:

AN:

82478

European-Finnish (FIN)

AF:

0.0000195

AC:

AN:

51396

Middle Eastern (MID)

AF:

0.00374

AC:

AN:

5608

European-Non Finnish (NFE)

AF:

0.000176

AC:

192

AN:

1088184

Other (OTH)

AF:

0.00255

AC:

150

AN:

58856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

143

215

286

358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00875

AC:

1332

AN:

152236

Hom.:

Cov.:

AF XY:

0.00852

AC XY:

634

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0292

AC:

1212

AN:

41524

American (AMR)

AF:

0.00569

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68028

Other (OTH)

AF:

0.00663

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

136

204

272

340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00344

Hom.:

Bravo

AF:

0.0103

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 26, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

c.1839+7G>A in intron 9 of GPR98: This variant is not expected to have clinical significance because it has been identified in 2.8% (82/2974) of African America n chromosomes in a broad population by the NHLBI Exome sequencing project (http: //evs.gs.washington.edu/EVS/; rs142011700). -

Aug 27, 2013

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 06, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:4

Feb 22, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 21, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Usher syndrome type 2C

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.5

(source)

DANN

Benign

0.31

PhyloP100

0.47

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000016

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over