NM_001364857.2:c.4735G>A

Variant names:

• chr1-31727443-C-T
• rs147230286
• NM_001364857.2:c.4735G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001364857.2(ADGRB2):​c.4735G>A​(p.Gly1579Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,587,494 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: ADGRB2 NM_001364857.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.27
• Publications: 3 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012290329).
• BP6: Variant 1-31727443-C-T is Benign according to our data. Variant chr1-31727443-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2887982.Status of the report is criteria_provided_single_submitter, 1 stars.

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.4735G>A	p.Gly1579Ser	missense	Exon 33 of 33	NP_001351786.1	O60241-1
	ADGRB2	NM_001294335.2		c.4732G>A	p.Gly1578Ser	missense	Exon 33 of 33	NP_001281264.1	O60241-2
	ADGRB2	NM_001294336.2		c.4633G>A	p.Gly1545Ser	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.4735G>A	p.Gly1579Ser	missense	Exon 33 of 33	ENSP00000362762.3	O60241-1
	ADGRB2	ENST00000373655.6	TSL:1	c.4732G>A	p.Gly1578Ser	missense	Exon 33 of 33	ENSP00000362759.2	O60241-2
	ADGRB2	ENST00000527361.5	TSL:1	c.4633G>A	p.Gly1545Ser	missense	Exon 30 of 30	ENSP00000435397.1	O60241-4

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000448 AC: 100 AN: 223136 AF XY: 0.000369

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00229

Gnomad ASJ exome AF: 0.00286

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000191

Gnomad OTH exome AF: 0.00248

GnomAD4 exome AF: 0.000118 AC: 169 AN: 1435320 Hom.: 1 Cov.: 31 AF XY: 0.000120 AC XY: 86 AN XY: 714278

African (AFR) AF: 0.00 AC: 0 AN: 31334

American (AMR) AF: 0.00189 AC: 68 AN: 35998

Ashkenazi Jewish (ASJ) AF: 0.00256 AC: 64 AN: 24974

East Asian (EAS) AF: 0.00 AC: 0 AN: 38406

South Asian (SAS) AF: 0.00 AC: 0 AN: 82146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 0.0000199 AC: 22 AN: 1104410

Other (OTH) AF: 0.000254 AC: 15 AN: 59164

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74332

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00137 AC: 21 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000202 Hom.: 0

Bravo AF: 0.000291

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000519 AC: 63

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
Eigen	Benign	0.13
Eigen_PC	Benign	-0.017
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.3
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.053
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.21
MVP		0.51
MPC		0.81
ClinPred		0.19	T
GERP RS		3.1
Varity_R		0.29
gMVP		0.37
Mutation Taster		=85/15	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: rs147230286; hg19: chr1-32193044;