chr6-68880064-G-A

Position:

• chr6-68880064-G-A

Variant summary

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

The NM_001704.3(ADGRB3):​c.758-50495G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0937 in 152,098 control chromosomes in the GnomAD database, including 884 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 0.094 (884 hom., cov: 32)
• Consequence: ADGRB3 NM_001704.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRB3	NM_001704.3	c.758-50495G>A		intron_variant		ENST00000370598.6	NP_001695.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRB3	ENST00000370598.6	c.758-50495G>A		intron_variant		1	NM_001704.3	ENSP00000359630	P1
ADGRB3	ENST00000546190.5	c.758-50495G>A		intron_variant		1		ENSP00000441821	P1
ADGRB3	ENST00000684661.1	c.758-50495G>A		intron_variant, NMD_transcript_variant				ENSP00000507613

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14260 AN: 151980 Hom.: 884 Cov.: 32

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0751

Gnomad ASJ AF: 0.0478

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.0858

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

GnomAD4 genome AF: 0.0937 AC: 14250 AN: 152098 Hom.: 884 Cov.: 32 AF XY: 0.0964 AC XY: 7168 AN XY: 74342

Gnomad4 AFR AF: 0.0235

Gnomad4 AMR AF: 0.0748

Gnomad4 ASJ AF: 0.0478

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.0844

Alfa AF: 0.112 Hom.: 199

Bravo AF: 0.0789

Asia WGS AF: 0.0470 AC: 162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.68
DANN	Benign	0.63

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: rs1880177; hg19: chr6-69589956;