chr1-31728043-G-C

Variant names:

• chr1-31728043-G-C
• rs146421594
• NM_001364857.2:c.4554C>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001364857.2(ADGRB2):​c.4554C>G​(p.Ala1518Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000793 in 1,584,684 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00060 (4 hom.)
• Consequence: ADGRB2 NM_001364857.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.290
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 1-31728043-G-C is Benign according to our data. Variant chr1-31728043-G-C is described in ClinVar as Benign. ClinVar VariationId is 718417.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.29 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 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.4554C>G	p.Ala1518Ala	synonymous	Exon 32 of 33	NP_001351786.1	O60241-1
	ADGRB2	NM_001294335.2		c.4551C>G	p.Ala1517Ala	synonymous	Exon 32 of 33	NP_001281264.1	O60241-2
	ADGRB2	NM_001294336.2		c.4452C>G	p.Ala1484Ala	synonymous	Exon 31 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.4554C>G	p.Ala1518Ala	synonymous	Exon 32 of 33	ENSP00000362762.3	O60241-1
	ADGRB2	ENST00000373655.6	TSL:1	c.4551C>G	p.Ala1517Ala	synonymous	Exon 32 of 33	ENSP00000362759.2	O60241-2
	ADGRB2	ENST00000527361.5	TSL:1	c.4452C>G	p.Ala1484Ala	synonymous	Exon 29 of 30	ENSP00000435397.1	O60241-4

Frequencies

GnomAD3 genomes AF: 0.00260 AC: 395 AN: 152030 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00797

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000757 AC: 155 AN: 204836 AF XY: 0.000503

Gnomad AFR exome AF: 0.00822

Gnomad AMR exome AF: 0.000657

Gnomad ASJ exome AF: 0.000109

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000732

Gnomad NFE exome AF: 0.000253

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.000598 AC: 857 AN: 1432536 Hom.: 4 Cov.: 30 AF XY: 0.000550 AC XY: 391 AN XY: 710998

African (AFR) AF: 0.0111 AC: 368 AN: 33020

American (AMR) AF: 0.000898 AC: 37 AN: 41194

Ashkenazi Jewish (ASJ) AF: 0.0000390 AC: 1 AN: 25618

East Asian (EAS) AF: 0.00 AC: 0 AN: 38504

South Asian (SAS) AF: 0.0000360 AC: 3 AN: 83246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45384

Middle Eastern (MID) AF: 0.00605 AC: 32 AN: 5290

European-Non Finnish (NFE) AF: 0.000296 AC: 326 AN: 1100892

Other (OTH) AF: 0.00152 AC: 90 AN: 59388

GnomAD4 genome AF: 0.00263 AC: 400 AN: 152148 Hom.: 5 Cov.: 32 AF XY: 0.00259 AC XY: 193 AN XY: 74382

African (AFR) AF: 0.00805 AC: 334 AN: 41516

American (AMR) AF: 0.00281 AC: 43 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 67976

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.000245 Hom.: 0

Bravo AF: 0.00321

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.1
DANN	Benign	0.58
PhyloP100		-0.29
Mutation Taster		=100/0	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: rs146421594; hg19: chr1-32193644;