rs780180737

chr5-90706400-ACT-Achr5-90706400-ACT-ACTCT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

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. 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
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:5
• Conservation: PhyloP100: -0.0200

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 -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=5, 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	UniProt
ADGRV1	NM_032119.4	c.8730+9_8730+10del		splice_region_variant, intron_variant		ENST00000405460.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRV1	ENST00000405460.9	c.8730+9_8730+10del		splice_region_variant, intron_variant		1	NM_032119.4	P1

Frequencies

GnomAD3 genomes AF: 0.00325 AC: 263 AN: 81038 Hom.: 9 Cov.: 30

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.: 6 AF XY: 0.00477 AC XY: 326 AN XY: 68316

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.: 3 AF XY: 0.000903 AC XY: 628 AN XY: 695212

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.: 9 Cov.: 30 AF XY: 0.00337 AC XY: 132 AN XY: 39212

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.: 0

Asia WGS AF: 0.0130 AC: 44 AN: 3460

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:5

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1 Benign:3

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

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 condition Benign:1

Benign, criteria provided, single submitter

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

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: rs780180737; hg19: chr5-90002217;