Variant 8-142475531-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001702.3(ADGRB1):c.842T>G(p.Leu281Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000263 in 1,139,750 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000026 ( 0 hom. )

Consequence

ADGRB1
NM_001702.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.78

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:

LOC124902075 (HGNC:):

LOC124902075 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRB1	NM_001702.3 linkuse as main transcript	c.842T>G	p.Leu281Arg	missense_variant	3/31	ENST00000517894.6	NP_001693.2	O14514

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADGRB1	ENST00000517894.6 linkuse as main transcript	c.842T>G	p.Leu281Arg	missense_variant	3/31	5	NM_001702.3	ENSP00000430945.1	O14514
ADGRB1	ENST00000521208.5 linkuse as main transcript	n.842T>G		non_coding_transcript_exon_variant	3/30	5		ENSP00000427783.1	E5RG74
ADGRB1	ENST00000643448.1 linkuse as main transcript	c.842T>G	p.Leu281Arg	missense_variant	3/31			ENSP00000494563.1	A0A2R8Y5M7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000118

AC:

AN:

84954

Hom.:

AF XY:

0.0000205

AC XY:

AN XY:

48724

show subpopulations

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:

0.0000204

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000263

AC:

AN:

1139750

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

545148

show subpopulations

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:

0.00000315

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000921

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

Apr 11, 2023

The c.842T>G (p.L281R) alteration is located in exon 2 (coding exon 2) of the ADGRB1 gene. This alteration results from a T to G substitution at nucleotide position 842, causing the leucine (L) at amino acid position 281 to be replaced by an arginine (R). 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

Benign

0.25

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

.;T;T

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.63

LIST_S2

Uncertain

0.92

D;.;D

M_CAP

Benign

0.078

MetaRNN

Uncertain

0.48

T;T;T

MetaSVM

Benign

-0.79

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.2

.;D;D

REVEL

Benign

0.29

Sift

Uncertain

0.0010

.;D;D

Sift4G

Pathogenic

0.0010

.;D;D

Vest4

0.72, 0.61

MutPred

0.64

Gain of disorder (P = 0.0271);Gain of disorder (P = 0.0271);Gain of disorder (P = 0.0271);

MVP

0.068

MPC

2.2

ClinPred

0.75

GERP RS

4.5

Varity_R

0.94

gMVP

0.67

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