Variant rs780180737 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_032119.4(ADGRV1):c.8730+9_8730+10del variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,485,070 control chromosomes in the GnomAD database, including 12 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0032 ( 9 hom., cov: 30)

Exomes 𝑓: 0.00092 ( 3 hom. )

Consequence

ADGRV1
NM_032119.4 splice_region, intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: -0.0200

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 -9 ACMG points.

BP6

Variant 5-90706400-ACT-A is Benign according to our data. Variant chr5-90706400-ACT-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 46398.We mark this variant Likely_benign, oryginal submissions are: {Benign=4, Uncertain_significance=1}. Variant chr5-90706400-ACT-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4 linkuse as main transcript	c.8730+9_8730+10del		splice_region_variant, intron_variant		ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9 linkuse as main transcript	c.8730+9_8730+10del		splice_region_variant, intron_variant		1	NM_032119.4	ENSP00000384582	P1	Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.00325

AC:

263

AN:

81038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000256

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00240

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0986

Gnomad SAS

AF:

0.00308

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000226

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00515

AC:

648

AN:

125930

Hom.:

AF XY:

0.00477

AC XY:

326

AN XY:

68316

show subpopulations

Gnomad AFR exome

AF:

0.000278

Gnomad AMR exome

AF:

0.000196

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0765

Gnomad SAS exome

AF:

0.000396

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000166

Gnomad OTH exome

AF:

0.00256

GnomAD4 exome

AF:

0.000925

AC:

1298

AN:

1403996

Hom.:

AF XY:

0.000903

AC XY:

628

AN XY:

695212

show subpopulations

Gnomad4 AFR exome

AF:

0.000164

Gnomad4 AMR exome

AF:

0.0000925

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0293

Gnomad4 SAS exome

AF:

0.000400

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000129

Gnomad4 OTH exome

AF:

0.00219

GnomAD4 genome

AF:

0.00323

AC:

262

AN:

81074

Hom.:

Cov.:

AF XY:

0.00337

AC XY:

132

AN XY:

39212

show subpopulations

Gnomad4 AFR

AF:

0.000255

Gnomad4 AMR

AF:

0.00240

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0988

Gnomad4 SAS

AF:

0.00308

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000226

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.000590

Hom.:

Asia WGS

AF:

0.0130

AC:

AN:

3460

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:3

Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 12, 2016	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 18, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 05, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jul 23, 2012

- -

ADGRV1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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