6-68980675-A-G

Variant names:

• chr6-68980675-A-G
• rs12665384
• NM_001704.3:c.1734+5335A>G

Variant summary

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

The NM_001704.3(ADGRB3):​c.1734+5335A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 151,600 control chromosomes in the GnomAD database, including 2,005 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 0.11 (2005 hom., cov: 32)
• Consequence: ADGRB3 NM_001704.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.642
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001704.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRB3	NM_001704.3	MANE Select	c.1734+5335A>G		intron	N/A	NP_001695.2	O60242-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRB3	ENST00000370598.6	TSL:1 MANE Select	c.1734+5335A>G		intron	N/A	ENSP00000359630.1	O60242-1
	ADGRB3	ENST00000546190.5	TSL:1	c.1734+5335A>G		intron	N/A	ENSP00000441821.2	O60242-1
	ADGRB3	ENST00000684661.1		n.1734+5335A>G		intron	N/A	ENSP00000507613.1	A0A804HJR2

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16169 AN: 151480 Hom.: 1998 Cov.: 32

Gnomad AFR AF: 0.0354

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.0704

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.135

Gnomad NFE AF: 0.0898

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.107 AC: 16194 AN: 151600 Hom.: 2005 Cov.: 32 AF XY: 0.113 AC XY: 8347 AN XY: 74062

African (AFR) AF: 0.0354 AC: 1470 AN: 41536

American (AMR) AF: 0.170 AC: 2576 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.0704 AC: 243 AN: 3450

East Asian (EAS) AF: 0.566 AC: 2925 AN: 5168

South Asian (SAS) AF: 0.198 AC: 958 AN: 4828

European-Finnish (FIN) AF: 0.131 AC: 1378 AN: 10516

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 290

European-Non Finnish (NFE) AF: 0.0898 AC: 6079 AN: 67684

Other (OTH) AF: 0.134 AC: 279 AN: 2086

Alfa AF: 0.0999 Hom.: 2058

Bravo AF: 0.109

Asia WGS AF: 0.401 AC: 1392 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.5
DANN	Benign	0.46
PhyloP100		0.64
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: rs12665384; hg19: chr6-69690567;