rs371019516

Variant names:

• chr5-90703681-C-A
• rs371019516
• NM_032119.4:c.8172C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-90703681-C-A
• chr5-90703681-C-G
• chr5-90703681-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032119.4(ADGRV1):​c.8172C>A​(p.Phe2724Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ADGRV1 NM_032119.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.582

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.090082854).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.8172C>A	p.Phe2724Leu	missense_variant	Exon 35 of 90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.8172C>A	p.Phe2724Leu	missense_variant	Exon 35 of 90	1	NM_032119.4	ENSP00000384582.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000420 AC: 1 AN: 237914 Hom.: 0 AF XY: 0.00000776 AC XY: 1 AN XY: 128920

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000926

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447460 Hom.: 0 Cov.: 27 AF XY: 0.00000139 AC XY: 1 AN XY: 719770

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.07e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.66
DEOGEN2	Benign	0.045	T;T;.
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.72	.;T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.090	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.57	.;N;.
REVEL	Benign	0.12
Sift	Benign	0.81	.;T;.
Sift4G	Benign	0.64	.;T;.
Polyphen		0.0090	B;B;.
Vest4		0.40
MutPred		0.38		Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);.;
MVP		0.29
MPC		0.28
ClinPred		0.12	T
GERP RS		1.2
Varity_R		0.091
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs371019516; hg19: chr5-89999498;