chr1-31727462-C-A

Variant names:

• chr1-31727462-C-A
• rs149701008
• NM_001364857.2:c.4716G>T

Variant summary

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

The NM_001364857.2(ADGRB2):​c.4716G>T​(p.Glu1572Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,438,564 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. Synonymous variant affecting the same amino acid position (i.e. E1572E) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ADGRB2 NM_001364857.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185

Genes affected

ADGRB2 (HGNC:944): (adhesion G protein-coupled receptor B2) This gene encodes a a seven-span transmembrane protein that is thought to be a member of the secretin receptor family. The encoded protein is a brain-specific inhibitor of angiogenesis. The mature peptide may be further cleaved into additional products (PMID:20367554). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

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=0.15503657).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRB2	NM_001364857.2	c.4716G>T	p.Glu1572Asp	missense_variant	Exon 33 of 33	ENST00000373658.8	NP_001351786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRB2	ENST00000373658.8	c.4716G>T	p.Glu1572Asp	missense_variant	Exon 33 of 33	5	NM_001364857.2	ENSP00000362762.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000884 AC: 2 AN: 226298 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 123204

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: 0.0000188

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1438564 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 715806

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: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T;T;.;T;T;.;T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.16	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.1	N;N;N;N;N;N;N
REVEL	Benign	0.034
Sift	Pathogenic	0.0	D;D;D;D;D;D;D
Sift4G	Benign	0.066	T;T;T;T;T;T;T
Polyphen		0.96, 0.77, 0.86	.;.;D;.;P;D;P
Vest4		0.16
MutPred		0.26		.;.;.;.;Loss of catalytic residue at E1572 (P = 0.0055);.;.;
MVP		0.31
MPC		0.83
ClinPred		0.83	D
GERP RS		3.1
Varity_R		0.40
gMVP		0.19

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: rs149701008; hg19: chr1-32193063;