rs35092519

Variant names:

• chr5-90778942-G-A
• rs35092519
• NM_032119.4:c.12927G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-90778942-G-A
• chr5-90778942-G-C
• chr5-90778942-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_032119.4(ADGRV1):​c.12927G>A​(p.Ala4309Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.025 in 1,613,416 control chromosomes in the GnomAD database, including 690 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A4309A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.035 (123 hom., cov: 32)
  • Exomes 𝑓: 0.024 (567 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.17
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 5-90778942-G-A is Benign according to our data. Variant chr5-90778942-G-A is described in ClinVar as Benign. ClinVar VariationId is 46264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.17 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.12927G>A	p.Ala4309Ala	synonymous_variant	Exon 64 of 90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.12927G>A	p.Ala4309Ala	synonymous_variant	Exon 64 of 90	1	NM_032119.4	ENSP00000384582.2
ADGRV1	ENST00000425867.3	c.1881G>A	p.Ala627Ala	synonymous_variant	Exon 12 of 38	5		ENSP00000392618.3
ADGRV1	ENST00000640464.1	n.3346G>A		non_coding_transcript_exon_variant	Exon 21 of 21	5
ADGRV1	ENST00000639431.1	n.265+102733G>A		intron_variant	Intron 2 of 4	5		ENSP00000491057.1

Frequencies

GnomAD3 genomes AF: 0.0351 AC: 5343 AN: 152078 Hom.: 124 Cov.: 32

Gnomad AFR AF: 0.0658

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0264

Gnomad ASJ AF: 0.0827

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.0183

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0238

Gnomad OTH AF: 0.0379

GnomAD2 exomes AF: 0.0239 AC: 5948 AN: 248854 AF XY: 0.0231

Gnomad AFR exome AF: 0.0650

Gnomad AMR exome AF: 0.0156

Gnomad ASJ exome AF: 0.0771

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0193

Gnomad NFE exome AF: 0.0253

Gnomad OTH exome AF: 0.0257

GnomAD4 exome AF: 0.0239 AC: 34922 AN: 1461220 Hom.: 567 Cov.: 31 AF XY: 0.0235 AC XY: 17106 AN XY: 726902

African (AFR) AF: 0.0652 AC: 2182 AN: 33442

American (AMR) AF: 0.0183 AC: 817 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.0765 AC: 1997 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00628 AC: 542 AN: 86244

European-Finnish (FIN) AF: 0.0182 AC: 974 AN: 53402

Middle Eastern (MID) AF: 0.0340 AC: 196 AN: 5760

European-Non Finnish (NFE) AF: 0.0238 AC: 26493 AN: 1111516

Other (OTH) AF: 0.0285 AC: 1721 AN: 60342

GnomAD4 genome AF: 0.0352 AC: 5351 AN: 152196 Hom.: 123 Cov.: 32 AF XY: 0.0341 AC XY: 2535 AN XY: 74426

African (AFR) AF: 0.0658 AC: 2734 AN: 41530

American (AMR) AF: 0.0263 AC: 402 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0827 AC: 287 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00581 AC: 28 AN: 4820

European-Finnish (FIN) AF: 0.0183 AC: 194 AN: 10612

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0238 AC: 1616 AN: 68000

Other (OTH) AF: 0.0375 AC: 79 AN: 2108

Alfa AF: 0.0293 Hom.: 48

Bravo AF: 0.0392

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.0305

EpiControl AF: 0.0307

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Jun 23, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 16, 2010

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 14, 2013

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. -

Usher syndrome type 2C Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Feb 03, 2025

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
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.046
DANN	Benign	0.56
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35092519; hg19: chr5-90074759; COSMIC: COSV67996341; COSMIC: COSV67996341;