6-69016470-C-T

Variant names:

• chr6-69016470-C-T
• rs9446085
• NM_001704.3:c.1999-1921C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001704.3(ADGRB3):​c.1999-1921C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,672 control chromosomes in the GnomAD database, including 14,372 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 0.42 (14372 hom., cov: 32)
• Consequence: ADGRB3 NM_001704.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRB3	NM_001704.3	c.1999-1921C>T		intron_variant	Intron 12 of 31	ENST00000370598.6	NP_001695.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRB3	ENST00000370598.6	c.1999-1921C>T		intron_variant	Intron 12 of 31	1	NM_001704.3	ENSP00000359630.1
ADGRB3	ENST00000546190.5	c.1999-1921C>T		intron_variant	Intron 10 of 29	1		ENSP00000441821.2
ADGRB3	ENST00000684661.1	n.1999-1921C>T		intron_variant	Intron 12 of 31			ENSP00000507613.1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64393 AN: 151554 Hom.: 14363 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.0370

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.425 AC: 64419 AN: 151672 Hom.: 14372 Cov.: 32 AF XY: 0.421 AC XY: 31232 AN XY: 74106

African (AFR) AF: 0.469 AC: 19423 AN: 41400

American (AMR) AF: 0.318 AC: 4830 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1973 AN: 3468

East Asian (EAS) AF: 0.0371 AC: 191 AN: 5150

South Asian (SAS) AF: 0.315 AC: 1517 AN: 4820

European-Finnish (FIN) AF: 0.457 AC: 4833 AN: 10570

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30309 AN: 67764

Other (OTH) AF: 0.417 AC: 879 AN: 2110

Alfa AF: 0.334 Hom.: 1370

Bravo AF: 0.414

Asia WGS AF: 0.171 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.61
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9446085; hg19: chr6-69726362;