NM_001364857.2:c.4716G>A

Variant names:

• chr1-31727462-C-T
• rs149701008
• NM_001364857.2:c.4716G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_001364857.2(ADGRB2):​c.4716G>A​(p.Glu1572Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00496 in 1,590,850 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (38 hom.)
• Consequence: ADGRB2 NM_001364857.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.185
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 1-31727462-C-T is Benign according to our data. Variant chr1-31727462-C-T is described in ClinVar as Benign. ClinVar VariationId is 773632.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.185 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00442 (673/152298) while in subpopulation EAS AF = 0.0343 (178/5184). AF 95% confidence interval is 0.0302. There are 7 homozygotes in GnomAd4. There are 309 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364857.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRB2	NM_001364857.2	MANE Select	c.4716G>A	p.Glu1572Glu	synonymous	Exon 33 of 33	NP_001351786.1	O60241-1
	ADGRB2	NM_001294335.2		c.4713G>A	p.Glu1571Glu	synonymous	Exon 33 of 33	NP_001281264.1	O60241-2
	ADGRB2	NM_001294336.2		c.4614G>A	p.Glu1538Glu	synonymous	Exon 32 of 32	NP_001281265.1	O60241-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRB2	ENST00000373658.8	TSL:5 MANE Select	c.4716G>A	p.Glu1572Glu	synonymous	Exon 33 of 33	ENSP00000362762.3	O60241-1
	ADGRB2	ENST00000373655.6	TSL:1	c.4713G>A	p.Glu1571Glu	synonymous	Exon 33 of 33	ENSP00000362759.2	O60241-2
	ADGRB2	ENST00000527361.5	TSL:1	c.4614G>A	p.Glu1538Glu	synonymous	Exon 30 of 30	ENSP00000435397.1	O60241-4

Frequencies

GnomAD3 genomes AF: 0.00442 AC: 672 AN: 152180 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.0343

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00480

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00513

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00611 AC: 1382 AN: 226298 AF XY: 0.00597

Gnomad AFR exome AF: 0.000654

Gnomad AMR exome AF: 0.000520

Gnomad ASJ exome AF: 0.000453

Gnomad EAS exome AF: 0.0348

Gnomad FIN exome AF: 0.00561

Gnomad NFE exome AF: 0.00575

Gnomad OTH exome AF: 0.00388

GnomAD4 exome AF: 0.00502 AC: 7218 AN: 1438552 Hom.: 38 Cov.: 31 AF XY: 0.00488 AC XY: 3492 AN XY: 715804

African (AFR) AF: 0.000727 AC: 23 AN: 31646

American (AMR) AF: 0.000817 AC: 30 AN: 36724

Ashkenazi Jewish (ASJ) AF: 0.000399 AC: 10 AN: 25046

East Asian (EAS) AF: 0.0200 AC: 773 AN: 38726

South Asian (SAS) AF: 0.00151 AC: 125 AN: 82556

European-Finnish (FIN) AF: 0.00531 AC: 283 AN: 53246

Middle Eastern (MID) AF: 0.000880 AC: 5 AN: 5684

European-Non Finnish (NFE) AF: 0.00508 AC: 5616 AN: 1105590

Other (OTH) AF: 0.00595 AC: 353 AN: 59334

GnomAD4 genome AF: 0.00442 AC: 673 AN: 152298 Hom.: 7 Cov.: 32 AF XY: 0.00415 AC XY: 309 AN XY: 74468

African (AFR) AF: 0.000770 AC: 32 AN: 41550

American (AMR) AF: 0.00229 AC: 35 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.0343 AC: 178 AN: 5184

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4824

European-Finnish (FIN) AF: 0.00480 AC: 51 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00513 AC: 349 AN: 68028

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00447 Hom.: 2

Bravo AF: 0.00396

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	6.6
DANN	Benign	0.53
PhyloP100		0.18
Mutation Taster		=99/1	polymorphism

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: rs149701008; hg19: chr1-32193063;