5-90866468-T-C

Variant names:

• chr5-90866468-T-C
• rs2438345
• NM_032119.4:c.17856+2611T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032119.4(ADGRV1):​c.17856+2611T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 151,674 control chromosomes in the GnomAD database, including 27,608 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (27608 hom., cov: 30)
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.644
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.17856+2611T>C		intron_variant	Intron 83 of 89	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.17856+2611T>C		intron_variant	Intron 83 of 89	1	NM_032119.4	ENSP00000384582.2

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90745 AN: 151556 Hom.: 27590 Cov.: 30

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.617

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.599 AC: 90813 AN: 151674 Hom.: 27608 Cov.: 30 AF XY: 0.605 AC XY: 44858 AN XY: 74114

African (AFR) AF: 0.545 AC: 22542 AN: 41340

American (AMR) AF: 0.716 AC: 10886 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1738 AN: 3470

East Asian (EAS) AF: 0.828 AC: 4269 AN: 5154

South Asian (SAS) AF: 0.692 AC: 3317 AN: 4796

European-Finnish (FIN) AF: 0.622 AC: 6561 AN: 10552

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39525 AN: 67850

Other (OTH) AF: 0.621 AC: 1311 AN: 2110

Alfa AF: 0.496 Hom.: 2011

Bravo AF: 0.602

Asia WGS AF: 0.775 AC: 2692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.72
PhyloP100		0.64
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2438345; hg19: chr5-90162285; COSMIC: COSV67981258;