6-68971768-T-C

Position:

• chr6-68971768-T-C

Variant summary

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

The NM_001704.3(ADGRB3):​c.1526-2995T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 152,186 control chromosomes in the GnomAD database, including 19,446 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 0.49 (19446 hom., cov: 34)
• Consequence: ADGRB3 NM_001704.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRB3	NM_001704.3	c.1526-2995T>C		intron_variant		ENST00000370598.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRB3	ENST00000370598.6	c.1526-2995T>C		intron_variant		1	NM_001704.3	P1
ADGRB3	ENST00000546190.5	c.1526-2995T>C		intron_variant		1		P1
ADGRB3	ENST00000684661.1	c.1526-2995T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74655 AN: 152068 Hom.: 19408 Cov.: 34

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.491 AC: 74744 AN: 152186 Hom.: 19446 Cov.: 34 AF XY: 0.488 AC XY: 36327 AN XY: 74400

Gnomad4 AFR AF: 0.653

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.498

Alfa AF: 0.405 Hom.: 6266

Bravo AF: 0.506

Asia WGS AF: 0.557 AC: 1938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.082
DANN	Benign	0.34

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: rs3798979; hg19: chr6-69681660;