rs2022212

Positions:

• chr6-68822065-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001704.3(ADGRB3):​c.758-108494A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 151,830 control chromosomes in the GnomAD database, including 2,562 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 0.14 (2562 hom., cov: 32)
• Consequence: ADGRB3 NM_001704.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.989

Genes affected

ADGRB3 (HGNC:945): (adhesion G protein-coupled receptor B3) This p53-target gene encodes a brain-specific angiogenesis inhibitor, a seven-span transmembrane protein, and is thought to be a member of the secretin receptor family. Brain-specific angiogenesis proteins BAI2 and BAI3 are similar to BAI1 in structure, have similar tissue specificities, and may also play a role in angiogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRB3	NM_001704.3	c.758-108494A>G		intron_variant		ENST00000370598.6	NP_001695.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRB3	ENST00000370598.6	c.758-108494A>G		intron_variant		1	NM_001704.3	ENSP00000359630.1
ADGRB3	ENST00000546190.5	c.758-108494A>G		intron_variant		1		ENSP00000441821.2
ADGRB3	ENST00000684661.1	n.758-108494A>G		intron_variant				ENSP00000507613.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21351 AN: 151712 Hom.: 2552 Cov.: 32

Gnomad AFR AF: 0.0565

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.0733

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.158

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.141 AC: 21381 AN: 151830 Hom.: 2562 Cov.: 32 AF XY: 0.146 AC XY: 10870 AN XY: 74202

Gnomad4 AFR AF: 0.0565

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.0733

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.163

Alfa AF: 0.131 Hom.: 2086

Bravo AF: 0.150

Asia WGS AF: 0.408 AC: 1412 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.25
DANN	Benign	0.59

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: rs2022212; hg19: chr6-69531957;