chr5-90629517-A-C

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.1817A>C(p.Asn606Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00155 in 1,611,358 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. N606N) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0087 ( 21 hom., cov: 31)

Exomes 𝑓: 0.00081 ( 15 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 6.86

Publications

4 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: Orphanet, ClinGen
Usher syndrome type 2C
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
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 (MetaRNN=0.009265631).

BP6

Variant 5-90629517-A-C is Benign according to our data. Variant chr5-90629517-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46296.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 = 0.00868 (1321/152238) while in subpopulation AFR AF = 0.0307 (1274/41542). AF 95% confidence interval is 0.0293. There are 21 homozygotes in GnomAd4. There are 597 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 21 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032119.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	NM_032119.4	MANE Select	c.1817A>C	p.Asn606Thr	missense	Exon 9 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.1916A>C		non_coding_transcript_exon	Exon 9 of 90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.1817A>C	p.Asn606Thr	missense	Exon 9 of 90	ENSP00000384582.2	Q8WXG9-1
ADGRV1	ENST00000504142.2	TSL:5	n.583A>C		non_coding_transcript_exon	Exon 3 of 14
ADGRV1	ENST00000640109.1	TSL:5	n.1913A>C		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes

AF:

0.00866

AC:

1317

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0307

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00718

GnomAD2 exomes

AF:

0.00218

AC:

537

AN:

246804

AF XY:

0.00163

show subpopulations

Gnomad AFR exome

AF:

0.0318

Gnomad AMR exome

AF:

0.00105

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000626

Gnomad OTH exome

AF:

0.000671

GnomAD4 exome

AF:

0.000810

AC:

1182

AN:

1459120

Hom.:

Cov.:

AF XY:

0.000708

AC XY:

514

AN XY:

725936

show subpopulations

African (AFR)

AF:

0.0293

AC:

975

AN:

33250

American (AMR)

AF:

0.00124

AC:

AN:

44372

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26006

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.0000349

AC:

AN:

86052

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53022

Middle Eastern (MID)

AF:

0.000695

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000288

AC:

AN:

1110766

Other (OTH)

AF:

0.00188

AC:

113

AN:

60228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

113

169

226

282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00868

AC:

1321

AN:

152238

Hom.:

Cov.:

AF XY:

0.00802

AC XY:

597

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0307

AC:

1274

AN:

41542

American (AMR)

AF:

0.00209

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00710

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

118

176

235

294

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:

0.00328

Hom.:

Bravo

AF:

0.00970

ESP6500AA

AF:

0.0328

AC:

121

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.00277

AC:

335

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Febrile seizures, familial, 4;C2931213:Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0093

MetaSVM

Benign

-0.89

PhyloP100

6.9

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.0

REVEL

Benign

0.22

Sift

Benign

0.57

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.78

MVP

0.78

MPC

0.23

ClinPred

0.026

GERP RS

5.5

Varity_R

0.24

gMVP

0.76

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over