chr1-31727499-C-T

Variant names:

• chr1-31727499-C-T
• rs747810006
• NM_001364857.2:c.4679G>A

Variant summary

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

The NM_001364857.2(ADGRB2):​c.4679G>A​(p.Arg1560Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,596,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000097 (0 hom.)
• Consequence: ADGRB2 NM_001364857.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 2.80
• Publications: 0 publications found

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

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=0.13294572).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364857.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRB2	NM_001364857.2	MANE Select	c.4679G>A	p.Arg1560Gln	missense	Exon 33 of 33	NP_001351786.1	O60241-1
	ADGRB2	NM_001294335.2		c.4676G>A	p.Arg1559Gln	missense	Exon 33 of 33	NP_001281264.1	O60241-2
	ADGRB2	NM_001294336.2		c.4577G>A	p.Arg1526Gln	missense	Exon 32 of 32	NP_001281265.1	O60241-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRB2	ENST00000373658.8	TSL:5 MANE Select	c.4679G>A	p.Arg1560Gln	missense	Exon 33 of 33	ENSP00000362762.3	O60241-1
	ADGRB2	ENST00000373655.6	TSL:1	c.4676G>A	p.Arg1559Gln	missense	Exon 33 of 33	ENSP00000362759.2	O60241-2
	ADGRB2	ENST00000527361.5	TSL:1	c.4577G>A	p.Arg1526Gln	missense	Exon 30 of 30	ENSP00000435397.1	O60241-4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000215 AC: 5 AN: 232038 AF XY: 0.0000316

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000695

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000186

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000969 AC: 14 AN: 1444248 Hom.: 0 Cov.: 31 AF XY: 0.00000974 AC XY: 7 AN XY: 718772

African (AFR) AF: 0.00 AC: 0 AN: 32064

American (AMR) AF: 0.000103 AC: 4 AN: 38692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25342

East Asian (EAS) AF: 0.00 AC: 0 AN: 38824

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 0.00000723 AC: 8 AN: 1107136

Other (OTH) AF: 0.0000168 AC: 1 AN: 59640

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152118 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74310

African (AFR) AF: 0.00 AC: 0 AN: 41410

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.45
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.99	T
PhyloP100		2.8
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.057
Sift	Benign	0.078	T
Sift4G	Benign	0.33	T
Polyphen		0.99	D
Vest4		0.25
MutPred		0.20		Gain of methylation at K1558 (P = 0.0499)
MVP		0.082
MPC		1.0
ClinPred		0.47	T
GERP RS		4.2
Varity_R		0.17
gMVP		0.30
Mutation Taster		=78/22	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: rs747810006; hg19: chr1-32193100;