rs9294818

Positions:

• chr6-69062576-C-G

Variant summary

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

The NM_001704.3(ADGRB3):​c.2334-358C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 151,856 control chromosomes in the GnomAD database, including 144 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 0.032 (144 hom., cov: 31)
• Consequence: ADGRB3 NM_001704.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.700

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRB3	NM_001704.3	c.2334-358C>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.2334-358C>G		intron_variant		1	NM_001704.3	ENSP00000359630	P1
ADGRB3	ENST00000546190.5	c.2334-358C>G		intron_variant		1		ENSP00000441821	P1
ADGRB3	ENST00000684661.1	c.2334-358C>G		intron_variant, NMD_transcript_variant				ENSP00000507613

Frequencies

GnomAD3 genomes AF: 0.0319 AC: 4848 AN: 151738 Hom.: 144 Cov.: 31

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0793

Gnomad ASJ AF: 0.0312

Gnomad EAS AF: 0.0995

Gnomad SAS AF: 0.0187

Gnomad FIN AF: 0.0199

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0296

Gnomad OTH AF: 0.0346

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

GnomAD4 genome AF: 0.0320 AC: 4861 AN: 151856 Hom.: 144 Cov.: 31 AF XY: 0.0332 AC XY: 2466 AN XY: 74212

Gnomad4 AFR AF: 0.0157

Gnomad4 AMR AF: 0.0795

Gnomad4 ASJ AF: 0.0312

Gnomad4 EAS AF: 0.0995

Gnomad4 SAS AF: 0.0185

Gnomad4 FIN AF: 0.0199

Gnomad4 NFE AF: 0.0296

Gnomad4 OTH AF: 0.0342

Alfa AF: 0.0349 Hom.: 17

Bravo AF: 0.0372

Asia WGS AF: 0.0560 AC: 195 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.30

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: rs9294818; hg19: chr6-69772468;