rs745380273

Positions:

• chr5-90653951-C-A
• chr5-90653951-C-T

Variant summary

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

The ENST00000405460.9(ADGRV1):​c.4377C>A​(p.Asp1459Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D1459D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRV1 ENST00000405460.9 missense, splice_region
• Scores: Splicing: ADA: 0.0001786
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77

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=0.35609615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.4377C>A	p.Asp1459Glu	missense_variant, splice_region_variant	20/90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.4377C>A	p.Asp1459Glu	missense_variant, splice_region_variant	20/90	1	NM_032119.4	ENSP00000384582	P1
ADGRV1	ENST00000640403.1	c.1668C>A	p.Asp556Glu	missense_variant, splice_region_variant	10/29	5		ENSP00000492531
ADGRV1	ENST00000504142.2	n.3143C>A		non_coding_transcript_exon_variant	14/14	5
ADGRV1	ENST00000639676.1	n.1975C>A		splice_region_variant, non_coding_transcript_exon_variant	8/11	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T;T;.
Eigen	Benign	0.096
Eigen_PC	Benign	0.030
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.77	.;T;T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-0.34	T
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.1	.;N;.
REVEL	Uncertain	0.42
Sift	Uncertain	0.0060	.;D;.
Sift4G	Uncertain	0.012	.;D;.
Polyphen		1.0	D;D;.
Vest4		0.57
MutPred		0.36		Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);.;
MVP		0.64
MPC		0.30
ClinPred		0.95	D
GERP RS		0.30
Varity_R		0.30
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00018
dbscSNV1_RF	Benign	0.23
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: rs745380273; hg19: chr5-89949768;