rs688606

Positions:

• chr6-69074282-T-A
• chr6-69074282-T-C
• chr6-69074282-T-G

Variant summary

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

The NM_001704.3(ADGRB3):​c.2437-1713T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,062 control chromosomes in the GnomAD database, including 7,544 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 0.27 (7544 hom., cov: 31)
• Consequence: ADGRB3 NM_001704.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRB3	NM_001704.3	c.2437-1713T>A		intron_variant		ENST00000370598.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRB3	ENST00000370598.6	c.2437-1713T>A		intron_variant		1	NM_001704.3	P1
ADGRB3	ENST00000546190.5	c.2437-1713T>A		intron_variant		1		P1
ADGRB3	ENST00000684661.1	c.2437-1713T>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40567 AN: 151944 Hom.: 7528 Cov.: 31

Gnomad AFR AF: 0.0646

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.267 AC: 40591 AN: 152062 Hom.: 7544 Cov.: 31 AF XY: 0.276 AC XY: 20501 AN XY: 74316

Gnomad4 AFR AF: 0.0645

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.795

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.294

Alfa AF: 0.275 Hom.: 793

Bravo AF: 0.262

Asia WGS AF: 0.649 AC: 2256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.68

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: rs688606; hg19: chr6-69784174;