rs2206836

Positions:

• chr6-68751549-T-C
• chr6-68751549-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.757+112117T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,054 control chromosomes in the GnomAD database, including 44,159 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 0.76 (44159 hom., cov: 32)
• Consequence: ADGRB3 NM_001704.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205

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 = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRB3	NM_001704.3	c.757+112117T>C		intron_variant		ENST00000370598.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRB3	ENST00000370598.6	c.757+112117T>C		intron_variant		1	NM_001704.3	P1
ADGRB3	ENST00000546190.5	c.757+112117T>C		intron_variant		1		P1
ADGRB3	ENST00000684661.1	c.757+112117T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115457 AN: 151936 Hom.: 44112 Cov.: 32

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.809

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

GnomAD4 genome AF: 0.760 AC: 115563 AN: 152054 Hom.: 44159 Cov.: 32 AF XY: 0.755 AC XY: 56071 AN XY: 74312

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.792

Gnomad4 ASJ AF: 0.867

Gnomad4 EAS AF: 0.868

Gnomad4 SAS AF: 0.681

Gnomad4 FIN AF: 0.676

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.807

Alfa AF: 0.757 Hom.: 8425

Bravo AF: 0.775

Asia WGS AF: 0.751 AC: 2606 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	2.9
DANN	Benign	0.86

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: rs2206836; hg19: chr6-69461441;