Genetic Variant ADGRV1:c.8730+20_8730+21dupTT (chr5-90706403-C-CTT) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_032119.4(ADGRV1):c.8730+20_8730+21dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00851 in 1,355,026 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0095 ( 0 hom. )

Consequence

ADGRV1
NM_032119.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0450

Publications

3 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: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 5-90706403-C-CTT is Benign according to our data. Variant chr5-90706403-C-CTT is described in ClinVar as Benign. ClinVar VariationId is 1165478.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.8730+20_8730+21dupTT		intron_variant	Intron 38 of 89	ENST00000405460.9	NP_115495.3	Q8WXG9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9 link	c.8730+9_8730+10insTT		intron_variant	Intron 38 of 89	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.000225

AC:

AN:

146426

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000351

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000343

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000605

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000109

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000150

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0103

AC:

1148

AN:

111634

AF XY:

0.0104

show subpopulations

Gnomad AFR exome

AF:

0.0134

Gnomad AMR exome

AF:

0.0138

Gnomad ASJ exome

AF:

0.0116

Gnomad EAS exome

AF:

0.0126

Gnomad FIN exome

AF:

0.00459

Gnomad NFE exome

AF:

0.00980

Gnomad OTH exome

AF:

0.00799

GnomAD4 exome

AF:

0.00951

AC:

11493

AN:

1208528

Hom.:

Cov.:

AF XY:

0.00932

AC XY:

5571

AN XY:

597936

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0155

AC:

385

AN:

24878

American (AMR)

AF:

0.0107

AC:

251

AN:

23466

Ashkenazi Jewish (ASJ)

AF:

0.00994

AC:

208

AN:

20920

East Asian (EAS)

AF:

0.00886

AC:

290

AN:

32722

South Asian (SAS)

AF:

0.0111

AC:

704

AN:

63154

European-Finnish (FIN)

AF:

0.00538

AC:

243

AN:

45198

Middle Eastern (MID)

AF:

0.00863

AC:

AN:

4868

European-Non Finnish (NFE)

AF:

0.00940

AC:

8864

AN:

943038

Other (OTH)

AF:

0.0101

AC:

506

AN:

50284

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.255

Heterozygous variant carriers

1482

2963

4445

5926

7408

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

368

736

1104

1472

1840

<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:

0.000225

AC:

AN:

146498

Hom.:

Cov.:

AF XY:

0.000267

AC XY:

AN XY:

71250

show subpopulations

African (AFR)

AF:

0.000350

AC:

AN:

40030

American (AMR)

AF:

0.000342

AC:

AN:

14608

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3406

East Asian (EAS)

AF:

0.000607

AC:

AN:

4946

South Asian (SAS)

AF:

0.00

AC:

AN:

4612

European-Finnish (FIN)

AF:

0.000109

AC:

AN:

9200

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000150

AC:

AN:

66488

Other (OTH)

AF:

0.00

AC:

AN:

2010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

717

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 12, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.045

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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5-90706403-CTTTT-CTTTTTT

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