5-90653315-G-T

Variant names:

• chr5-90653315-G-T
• rs371571867
• NM_032119.4:c.3741G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032119.4(ADGRV1):​c.3741G>T​(p.Glu1247Asp) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E1247E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRV1 NM_032119.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.488
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13282588).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.3741G>T	p.Glu1247Asp	missense_variant	Exon 20 of 90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.3741G>T	p.Glu1247Asp	missense_variant	Exon 20 of 90	1	NM_032119.4	ENSP00000384582.2
ADGRV1	ENST00000640403.1	c.1032G>T	p.Glu344Asp	missense_variant	Exon 10 of 29	5		ENSP00000492531.1
ADGRV1	ENST00000504142.2	n.2507G>T		non_coding_transcript_exon_variant	Exon 14 of 14	5
ADGRV1	ENST00000639676.1	n.1339G>T		non_coding_transcript_exon_variant	Exon 8 of 11	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	T;T;.
Eigen	Benign	-0.046
Eigen_PC	Benign	0.071
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.58	.;T;T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.1	T
PhyloP100		0.49
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.11	.;N;.
REVEL	Benign	0.051
Sift	Benign	0.47	.;T;.
Sift4G	Benign	0.40	.;T;.
Polyphen		0.0040	B;B;.
Vest4		0.24
MutPred		0.44		Loss of disorder (P = 0.2969);Loss of disorder (P = 0.2969);.;
MVP		0.40
MPC		0.046
ClinPred		0.11	T
GERP RS		4.0
Varity_R		0.063
gMVP		0.27
Mutation Taster		=83/17	polymorphism

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: rs371571867; hg19: chr5-89949132;