8-142499525-C-T

Position:

• chr8-142499525-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ADGRB1	NM_001702.3	c.2675+8710C>T		intron_variant		ENST00000517894.6	NP_001693.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRB1	ENST00000517894.6	c.2675+8710C>T		intron_variant		5	NM_001702.3	ENSP00000430945.1
ADGRB1	ENST00000521208.5	n.2675+8710C>T		intron_variant		5		ENSP00000427783.1
ADGRB1	ENST00000643448.1	c.2666+8710C>T		intron_variant				ENSP00000494563.1
ADGRB1	ENST00000518820.1	n.1522+8710C>T		intron_variant		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

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.764

Gnomad4 EAS AF: 0.805

Gnomad4 SAS AF: 0.748

Gnomad4 FIN AF: 0.807

Gnomad4 NFE AF: 0.721

Gnomad4 OTH AF: 0.649

Alfa AF: 0.700 Hom.: 18783

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

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

Other links and lift over

dbSNP: rs11167147; hg19: chr8-143580886;