chr8-142464310-C-A

Position:

• chr8-142464310-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001702.3(ADGRB1):​c.112C>A​(p.Pro38Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000155 in 1,286,882 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: ADGRB1 NM_001702.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.58

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

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=0.4157006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRB1	NM_001702.3	c.112C>A	p.Pro38Thr	missense_variant	2/31	ENST00000517894.6	NP_001693.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRB1	ENST00000517894.6	c.112C>A	p.Pro38Thr	missense_variant	2/31	5	NM_001702.3	ENSP00000430945.1
ADGRB1	ENST00000521208.5	n.112C>A		non_coding_transcript_exon_variant	2/30	5		ENSP00000427783.1
ADGRB1	ENST00000643448.1	c.112C>A	p.Pro38Thr	missense_variant	2/31			ENSP00000494563.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000155 AC: 2 AN: 1286882 Hom.: 0 Cov.: 34 AF XY: 0.00000317 AC XY: 2 AN XY: 630296

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: 0.00000193

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 27, 2024

The c.112C>A (p.P38T) 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 112, causing the proline (P) at amino acid position 38 to be replaced by a threonine (T). 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	0.083
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	.;T;T
Eigen	Benign	0.090
Eigen_PC	Benign	0.034
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.70	T;.;T
M_CAP	Pathogenic	0.53	D
MetaRNN	Benign	0.42	T;T;T
MetaSVM	Benign	-0.87	T
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.4	.;D;D
REVEL	Benign	0.096
Sift	Uncertain	0.0080	.;D;D
Sift4G	Uncertain	0.0020	.;D;D
Vest4		0.28, 0.17
MutPred		0.35		Gain of catalytic residue at P38 (P = 0.0157);Gain of catalytic residue at P38 (P = 0.0157);Gain of catalytic residue at P38 (P = 0.0157);
MVP		0.17
MPC		1.6
ClinPred		0.95	D
GERP RS		4.5
Varity_R		0.17
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-143545671;