Variant chr1-31727584-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001364857.2(ADGRB2):c.4594C>T(p.Arg1532Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00903 in 1,548,822 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0093 ( 82 hom. )

Consequence

ADGRB2
NM_001364857.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.96

Variant links:

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]

ADGRB2 links:

ADGRB2 (HGNC:):

ADGRB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005131185).

BP6

Variant 1-31727584-G-A is Benign according to our data. Variant chr1-31727584-G-A is described in ClinVar as [Benign]. Clinvar id is 1598588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRB2	NM_001364857.2 linkuse as main transcript	c.4594C>T	p.Arg1532Cys	missense_variant	33/33	ENST00000373658.8	NP_001351786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRB2	ENST00000373658.8 linkuse as main transcript	c.4594C>T	p.Arg1532Cys	missense_variant	33/33	5	NM_001364857.2	ENSP00000362762.3		O60241-1

Frequencies

GnomAD3 genomes

AF:

0.00687

AC:

1044

AN:

152018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.0240

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0100

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00968

AC:

1751

AN:

180960

Hom.:

AF XY:

0.00934

AC XY:

914

AN XY:

97902

show subpopulations

Gnomad AFR exome

AF:

0.00164

Gnomad AMR exome

AF:

0.00106

Gnomad ASJ exome

AF:

0.000181

Gnomad EAS exome

AF:

0.0000723

Gnomad SAS exome

AF:

0.00123

Gnomad FIN exome

AF:

0.0269

Gnomad NFE exome

AF:

0.0133

Gnomad OTH exome

AF:

0.00892

GnomAD4 exome

AF:

0.00926

AC:

12939

AN:

1396686

Hom.:

Cov.:

AF XY:

0.00893

AC XY:

6177

AN XY:

691402

show subpopulations

Gnomad4 AFR exome

AF:

0.00119

Gnomad4 AMR exome

AF:

0.00133

Gnomad4 ASJ exome

AF:

0.000179

Gnomad4 EAS exome

AF:

0.000133

Gnomad4 SAS exome

AF:

0.00135

Gnomad4 FIN exome

AF:

0.0264

Gnomad4 NFE exome

AF:

0.0101

Gnomad4 OTH exome

AF:

0.00745

GnomAD4 genome

AF:

0.00686

AC:

1044

AN:

152136

Hom.:

Cov.:

AF XY:

0.00721

AC XY:

536

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.0240

Gnomad4 NFE

AF:

0.0100

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00875

Hom.:

Bravo

AF:

0.00497

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00895

AC:

ExAC

AF:

0.00986

AC:

1196

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2022	ADGRB2: BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.057

T;T;.;T;T;.;T

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.91

LIST_S2

Pathogenic

0.97

D;D;D;D;D;D;D

MetaRNN

Benign

0.0051

T;T;T;T;T;T;T

MetaSVM

Benign

-0.77

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.5

D;D;D;D;D;D;D

REVEL

Benign

0.12

Sift

Uncertain

0.0080

D;D;D;D;D;D;D

Sift4G

Uncertain

0.011

D;D;D;D;D;D;D

Polyphen

0.95, 1.0, 0.99

.;.;P;.;D;P;D

Vest4

0.24

MVP

0.15

MPC

1.1

ClinPred

0.021

GERP RS

3.3

Varity_R

0.16

gMVP

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over