5-90617923-C-T

Variant names:

• chr5-90617923-C-T
• rs61753944
• NM_032119.4:c.327C>T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_032119.4(ADGRV1):​c.327C>T​(p.Asp109Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00452 in 1,584,912 control chromosomes in the GnomAD database, including 206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (108 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (98 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.07

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]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 5-90617923-C-T is Benign according to our data. Variant chr5-90617923-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 46314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90617923-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.07 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.327C>T	p.Asp109Asp	synonymous_variant	Exon 3 of 90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.327C>T	p.Asp109Asp	synonymous_variant	Exon 3 of 90	1	NM_032119.4	ENSP00000384582.2

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 3367 AN: 152048 Hom.: 107 Cov.: 32

Gnomad AFR AF: 0.0751

Gnomad AMI AF: 0.0407

Gnomad AMR AF: 0.00865

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000662

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00537 AC: 1097 AN: 204438 Hom.: 33 AF XY: 0.00427 AC XY: 467 AN XY: 109270

Gnomad AFR exome AF: 0.0716

Gnomad AMR exome AF: 0.00312

Gnomad ASJ exome AF: 0.000545

Gnomad EAS exome AF: 0.00149

Gnomad SAS exome AF: 0.000358

Gnomad FIN exome AF: 0.000103

Gnomad NFE exome AF: 0.000633

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00264 AC: 3787 AN: 1432746 Hom.: 98 Cov.: 30 AF XY: 0.00237 AC XY: 1683 AN XY: 709656

Gnomad4 AFR exome AF: 0.0729

Gnomad4 AMR exome AF: 0.00382

Gnomad4 ASJ exome AF: 0.000548

Gnomad4 EAS exome AF: 0.000410

Gnomad4 SAS exome AF: 0.000392

Gnomad4 FIN exome AF: 0.0000193

Gnomad4 NFE exome AF: 0.000701

Gnomad4 OTH exome AF: 0.00613

GnomAD4 genome AF: 0.0222 AC: 3373 AN: 152166 Hom.: 108 Cov.: 32 AF XY: 0.0219 AC XY: 1632 AN XY: 74416

Gnomad4 AFR AF: 0.0750

Gnomad4 AMR AF: 0.00864

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000662

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.00907 Hom.: 23

Bravo AF: 0.0254

Asia WGS AF: 0.00520 AC: 19 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Mar 21, 2014

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. -

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Asp109Asp in Exon 03 of GPR98: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 6.5% (201/3098) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs61753944). -

not provided Benign:3

Nov 08, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: 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

- -

Jan 24, 2018

Athena Diagnostics

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: 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. -

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

Aug 13, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely 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	-0.33
CADD	Benign	11
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
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

LitVar

Other links and lift over

dbSNP: rs61753944; hg19: chr5-89913740; COSMIC: COSV67980701;