5-90637731-A-T

Variant names:

• chr5-90637731-A-T
• NM_032119.4:c.2023A>T

Variant summary

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

The NM_032119.4(ADGRV1):​c.2023A>T​(p.Ile675Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,988 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: 6.9e-7 (0 hom.)
• Consequence: ADGRV1 NM_032119.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40

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=0.34076038).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.2023A>T	p.Ile675Phe	missense_variant	Exon 11 of 90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.2023A>T	p.Ile675Phe	missense_variant	Exon 11 of 90	1	NM_032119.4	ENSP00000384582.2
ADGRV1	ENST00000504142.2	n.789A>T		non_coding_transcript_exon_variant	Exon 5 of 14	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452988 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 722856

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: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000553

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.64	.;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.8	.;N
REVEL	Benign	0.14
Sift	Benign	0.038	.;D
Sift4G	Uncertain	0.0080	.;D
Polyphen		0.97	D;D
Vest4		0.57
MutPred		0.41		Gain of catalytic residue at I675 (P = 0.0349);Gain of catalytic residue at I675 (P = 0.0349);
MVP		0.63
MPC		0.20
ClinPred		0.93	D
GERP RS		4.7
Varity_R		0.16
gMVP		0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-89933548;