8-142499525-C-T

Variant names:

• chr8-142499525-C-T
• rs11167147
• NM_001702.3:c.2675+8710C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001702.3(ADGRB1):​c.2675+8710C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 152,118 control chromosomes in the GnomAD database, including 31,258 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (31258 hom., cov: 34)
• Consequence: ADGRB1 NM_001702.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRB1	NM_001702.3	c.2675+8710C>T		intron_variant	Intron 17 of 30	ENST00000517894.6	NP_001693.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRB1	ENST00000517894.6	c.2675+8710C>T		intron_variant	Intron 17 of 30	5	NM_001702.3	ENSP00000430945.1
ADGRB1	ENST00000521208.5	n.2675+8710C>T		intron_variant	Intron 17 of 29	5		ENSP00000427783.1
ADGRB1	ENST00000643448.1	c.2666+8710C>T		intron_variant	Intron 17 of 30			ENSP00000494563.1
ADGRB1	ENST00000518820.1	n.1522+8710C>T		intron_variant	Intron 9 of 17	2

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92757 AN: 152000 Hom.: 31256 Cov.: 34

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.651

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.610 AC: 92784 AN: 152118 Hom.: 31258 Cov.: 34 AF XY: 0.619 AC XY: 46049 AN XY: 74368

African (AFR) AF: 0.293 AC: 12171 AN: 41496

American (AMR) AF: 0.684 AC: 10470 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 2651 AN: 3470

East Asian (EAS) AF: 0.805 AC: 4138 AN: 5140

South Asian (SAS) AF: 0.748 AC: 3608 AN: 4824

European-Finnish (FIN) AF: 0.807 AC: 8549 AN: 10598

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.721 AC: 48980 AN: 67964

Other (OTH) AF: 0.649 AC: 1374 AN: 2116

Alfa AF: 0.701 Hom.: 20735

Bravo AF: 0.587

Asia WGS AF: 0.744 AC: 2583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.64
DANN	Benign	0.76
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs11167147; hg19: chr8-143580886;