1-31728046-T-C

Position:

• chr1-31728046-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001364857.2(ADGRB2):​c.4551A>G​(p.Ala1517=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 1,585,246 control chromosomes in the GnomAD database, including 325,061 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (34421 hom., cov: 31)
  • Exomes 𝑓: 0.63 (290640 hom.)
• Consequence: ADGRB2 NM_001364857.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.34

Genes affected

ADGRB2 (HGNC:944): (adhesion G protein-coupled receptor B2) This gene encodes a a seven-span transmembrane protein that is thought to be a member of the secretin receptor family. The encoded protein is a brain-specific inhibitor of angiogenesis. The mature peptide may be further cleaved into additional products (PMID:20367554). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-31728046-T-C is Benign according to our data. Variant chr1-31728046-T-C is described in ClinVar as [Benign]. Clinvar id is 1596373.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRB2	NM_001364857.2	c.4551A>G	p.Ala1517=	synonymous_variant	32/33	ENST00000373658.8	NP_001351786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRB2	ENST00000373658.8	c.4551A>G	p.Ala1517=	synonymous_variant	32/33	5	NM_001364857.2	ENSP00000362762

Frequencies

GnomAD3 genomes AF: 0.665 AC: 100976 AN: 151804 Hom.: 34365 Cov.: 31

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.590

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.645

GnomAD3 exomes AF: 0.598 AC: 122790 AN: 205402 Hom.: 37793 AF XY: 0.601 AC XY: 67102 AN XY: 111602

Gnomad AFR exome AF: 0.795

Gnomad AMR exome AF: 0.493

Gnomad ASJ exome AF: 0.569

Gnomad EAS exome AF: 0.323

Gnomad SAS exome AF: 0.610

Gnomad FIN exome AF: 0.640

Gnomad NFE exome AF: 0.645

Gnomad OTH exome AF: 0.611

GnomAD4 exome AF: 0.633 AC: 907921 AN: 1433326 Hom.: 290640 Cov.: 83 AF XY: 0.633 AC XY: 450559 AN XY: 711378

Gnomad4 AFR exome AF: 0.798

Gnomad4 AMR exome AF: 0.503

Gnomad4 ASJ exome AF: 0.576

Gnomad4 EAS exome AF: 0.314

Gnomad4 SAS exome AF: 0.610

Gnomad4 FIN exome AF: 0.648

Gnomad4 NFE exome AF: 0.648

Gnomad4 OTH exome AF: 0.622

GnomAD4 genome AF: 0.665 AC: 101090 AN: 151920 Hom.: 34421 Cov.: 31 AF XY: 0.661 AC XY: 49064 AN XY: 74258

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.653

Gnomad4 OTH AF: 0.639

Alfa AF: 0.649 Hom.: 9655

Bravo AF: 0.663

Asia WGS AF: 0.516 AC: 1794 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1127100; hg19: chr1-32193647; COSMIC: COSV57071683;