8-142464329-C-A

Position:

chr8-142464329-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001702.3(ADGRB1):c.131C>A(p.Ala44Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000128 in 1,497,996 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 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

ADGRB1
NM_001702.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.60

Variant links:

Genes affected

ADGRB1 (HGNC:943): (adhesion G protein-coupled receptor B1) Angiogenesis is controlled by a local balance between stimulators and inhibitors of new vessel growth and is suppressed under normal physiologic conditions. Angiogenesis has been shown to be essential for growth and metastasis of solid tumors. In order to obtain blood supply for their growth, tumor cells are potently angiogenic and attract new vessels as results of increased secretion of inducers and decreased production of endogenous negative regulators. BAI1 contains at least one 'functional' p53-binding site within an intron, and its expression has been shown to be induced by wildtype p53. There are two other brain-specific angiogenesis inhibitor genes, designated BAI2 and BAI3 which along with BAI1 have similar tissue specificities and structures, however only BAI1 is transcriptionally regulated by p53. BAI1 is postulated to be a member of the secretin receptor family, an inhibitor of angiogenesis and a growth suppressor of glioblastomas [provided by RefSeq, Jul 2008]

ADGRB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.38449493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRB1	NM_001702.3 linkuse as main transcript	c.131C>A	p.Ala44Asp	missense_variant	2/31	ENST00000517894.6	NP_001693.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ADGRB1	ENST00000517894.6 linkuse as main transcript	c.131C>A	p.Ala44Asp	missense_variant	2/31	5	NM_001702.3	ENSP00000430945	P4
ADGRB1	ENST00000643448.1 linkuse as main transcript	c.131C>A	p.Ala44Asp	missense_variant	2/31			ENSP00000494563	A2
ADGRB1	ENST00000521208.5 linkuse as main transcript	c.131C>A	p.Ala44Asp	missense_variant, NMD_transcript_variant	2/30	5		ENSP00000427783

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000425

AC:

AN:

94030

Hom.:

AF XY:

0.0000189

AC XY:

AN XY:

52858

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000526

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:

0.0000870

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000137

AC:

184

AN:

1345886

Hom.:

Cov.:

AF XY:

0.000137

AC XY:

AN XY:

662888

show subpopulations

Gnomad4 AFR exome

AF:

0.0000364

Gnomad4 AMR exome

AF:

0.0000325

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000217

Gnomad4 NFE exome

AF:

0.000160

Gnomad4 OTH exome

AF:

0.0000714

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000270

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000651

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 02, 2022

The c.131C>A (p.A44D) alteration is located in exon 1 (coding exon 1) of the ADGRB1 gene. This alteration results from a C to A substitution at nucleotide position 131, causing the alanine (A) at amino acid position 44 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

.;T;T

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.74

T;.;T

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.38

T;T;T

MetaSVM

Benign

-0.85

MutationTaster

Benign

0.59

D;D

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.8

.;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0040

.;D;D

Sift4G

Pathogenic

0.0010

.;D;D

Vest4

0.21, 0.33

MVP

0.043

MPC

1.9

ClinPred

0.23

GERP RS

4.4

Varity_R

0.49

gMVP

0.63

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