Genetic Variant NM_032119.4:c.13599A>G (chr5-90784003-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032119.4(ADGRV1):c.13599A>G(p.Thr4533Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,610,940 control chromosomes in the GnomAD database, including 34,968 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2448 hom., cov: 32)

Exomes 𝑓: 0.20 ( 32520 hom. )

Consequence

ADGRV1
NM_032119.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.430

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 5-90784003-A-G is Benign according to our data. Variant chr5-90784003-A-G is described in ClinVar as [Benign]. Clinvar id is 46268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90784003-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.43 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.13599A>G	p.Thr4533Thr	synonymous_variant	Exon 67 of 90	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.13599A>G	p.Thr4533Thr	synonymous_variant	Exon 67 of 90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23447

AN:

152000

Hom.:

2447

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0404

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.279

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.223

Gnomad OTH

AF:

0.166

GnomAD3 exomes

AF:

0.162

AC:

40096

AN:

246750

Hom.:

4175

AF XY:

0.165

AC XY:

22116

AN XY:

133766

show subpopulations

Gnomad AFR exome

AF:

0.0362

Gnomad AMR exome

AF:

0.0963

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.00291

Gnomad SAS exome

AF:

0.101

Gnomad FIN exome

AF:

0.274

Gnomad NFE exome

AF:

0.222

Gnomad OTH exome

AF:

0.185

GnomAD4 exome

AF:

0.201

AC:

293874

AN:

1458822

Hom.:

32520

Cov.:

AF XY:

0.199

AC XY:

144460

AN XY:

725636

show subpopulations

Gnomad4 AFR exome

AF:

0.0342

Gnomad4 AMR exome

AF:

0.102

Gnomad4 ASJ exome

AF:

0.143

Gnomad4 EAS exome

AF:

0.00184

Gnomad4 SAS exome

AF:

0.103

Gnomad4 FIN exome

AF:

0.270

Gnomad4 NFE exome

AF:

0.225

Gnomad4 OTH exome

AF:

0.180

GnomAD4 genome

AF:

0.154

AC:

23449

AN:

152118

Hom.:

2448

Cov.:

AF XY:

0.154

AC XY:

11444

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0403

Gnomad4 AMR

AF:

0.139

Gnomad4 ASJ

AF:

0.136

Gnomad4 EAS

AF:

0.00308

Gnomad4 SAS

AF:

0.102

Gnomad4 FIN

AF:

0.279

Gnomad4 NFE

AF:

0.223

Gnomad4 OTH

AF:

0.169

Alfa

AF:

0.200

Hom.:

4156

Bravo

AF:

0.138

Asia WGS

AF:

0.0640

AC:

221

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Feb 26, 2016

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 23, 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

- -

Usher syndrome type 2C

Benign:2

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. -

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Benign:1

Dec 23, 2021

Fulgent Genetics, Fulgent Genetics

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

-0.80

CADD

Benign

5.4

DANN

Benign

0.72

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over