6-69010874-G-C

Position:

• chr6-69010874-G-C

Variant summary

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

The NM_001704.3(ADGRB3):​c.1930-3164G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,474 control chromosomes in the GnomAD database, including 13,154 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 0.41 (13154 hom., cov: 30)
• Consequence: ADGRB3 NM_001704.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.866

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRB3	NM_001704.3	c.1930-3164G>C		intron_variant		ENST00000370598.6	NP_001695.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRB3	ENST00000370598.6	c.1930-3164G>C		intron_variant		1	NM_001704.3	ENSP00000359630.1
ADGRB3	ENST00000546190.5	c.1930-3164G>C		intron_variant		1		ENSP00000441821.2
ADGRB3	ENST00000684661.1	n.1930-3164G>C		intron_variant				ENSP00000507613.1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61531 AN: 151362 Hom.: 13144 Cov.: 30

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.0375

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.406 AC: 61560 AN: 151474 Hom.: 13154 Cov.: 30 AF XY: 0.404 AC XY: 29886 AN XY: 73964

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.0376

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.404

Alfa AF: 0.411 Hom.: 1572

Bravo AF: 0.393

Asia WGS AF: 0.166 AC: 577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.5
DANN	Benign	0.69

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: rs9454674; hg19: chr6-69720766;