5-90701231-A-T

Variant names:

• chr5-90701231-A-T
• rs10514332
• NM_032119.4:c.8156-2434A>T

Variant summary

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

The NM_032119.4(ADGRV1):​c.8156-2434A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0601 in 152,160 control chromosomes in the GnomAD database, including 367 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 0.060 (367 hom., cov: 32)
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.8156-2434A>T		intron_variant	Intron 34 of 89	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.8156-2434A>T		intron_variant	Intron 34 of 89	1	NM_032119.4	ENSP00000384582.2

Frequencies

GnomAD3 genomes AF: 0.0602 AC: 9147 AN: 152042 Hom.: 369 Cov.: 32

Gnomad AFR AF: 0.0254

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0600

Gnomad ASJ AF: 0.0839

Gnomad EAS AF: 0.00539

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0485

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0808

Gnomad OTH AF: 0.0666

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

GnomAD4 genome AF: 0.0601 AC: 9140 AN: 152160 Hom.: 367 Cov.: 32 AF XY: 0.0601 AC XY: 4475 AN XY: 74400

African (AFR) AF: 0.0254 AC: 1054 AN: 41560

American (AMR) AF: 0.0599 AC: 916 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0839 AC: 291 AN: 3468

East Asian (EAS) AF: 0.00541 AC: 28 AN: 5180

South Asian (SAS) AF: 0.132 AC: 635 AN: 4824

European-Finnish (FIN) AF: 0.0485 AC: 514 AN: 10608

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0808 AC: 5488 AN: 67922

Other (OTH) AF: 0.0655 AC: 138 AN: 2108

Alfa AF: 0.0684 Hom.: 45

Bravo AF: 0.0562

Asia WGS AF: 0.0550 AC: 189 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.71
PhyloP100		-0.24
Mutation Taster		=100/0	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: rs10514332; hg19: chr5-89997048;