5-90658033-G-T

Position:

• chr5-90658033-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032119.4(ADGRV1):​c.4507G>T​(p.Ala1503Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,634 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ADGRV1 NM_032119.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.79

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31432146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.4507G>T	p.Ala1503Ser	missense_variant	21/90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.4507G>T	p.Ala1503Ser	missense_variant	21/90	1	NM_032119.4	ENSP00000384582.2
ADGRV1	ENST00000640403.1	c.1798G>T	p.Ala600Ser	missense_variant	11/29	5		ENSP00000492531.1
ADGRV1	ENST00000639676.1	n.2105G>T		non_coding_transcript_exon_variant	9/11	5
ADGRV1	ENST00000639473.1	n.-35G>T		upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000803 AC: 2 AN: 249212 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 135206

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461634 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727102

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;T;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.78	.;T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.92	T
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.6	.;N;.
REVEL	Benign	0.21
Sift	Benign	0.047	.;D;.
Sift4G	Uncertain	0.057	.;T;.
Polyphen		1.0	D;D;.
Vest4		0.34
MutPred		0.41		Gain of disorder (P = 0.0399);Gain of disorder (P = 0.0399);.;
MVP		0.61
MPC		0.26
ClinPred		0.67	D
GERP RS		5.0
Varity_R		0.20
gMVP		0.59

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: rs201391886; hg19: chr5-89953850; COSMIC: COSV105343715; COSMIC: COSV105343715;