6-73749014-A-G

Variant names:

• chr6-73749014-A-G
• rs9447004
• NM_133493.5:c.634-7629A>G

Variant summary

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

The NM_133493.5(CD109):​c.634-7629A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,970 control chromosomes in the GnomAD database, including 23,078 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 0.55 (23078 hom., cov: 31)
• Consequence: CD109 NM_133493.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 12 publications found

Genes affected

CD109 (HGNC:21685): (CD109 molecule) This gene encodes a glycosyl phosphatidylinositol (GPI)-linked glycoprotein that localizes to the surface of platelets, activated T-cells, and endothelial cells. The protein binds to and negatively regulates signalling by transforming growth factor beta (TGF-beta). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD109	NM_133493.5	c.634-7629A>G		intron_variant	Intron 5 of 32	ENST00000287097.6	NP_598000.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD109	ENST00000287097.6	c.634-7629A>G		intron_variant	Intron 5 of 32	1	NM_133493.5	ENSP00000287097.4
CD109	ENST00000437994.6	c.634-7629A>G		intron_variant	Intron 5 of 32	1		ENSP00000388062.2
CD109	ENST00000422508.6	c.403-7629A>G		intron_variant	Intron 4 of 31	1		ENSP00000404475.2
CD109	ENST00000649530.1	n.606-7629A>G		intron_variant	Intron 4 of 25

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82744 AN: 151850 Hom.: 23044 Cov.: 31

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.545 AC: 82830 AN: 151970 Hom.: 23078 Cov.: 31 AF XY: 0.538 AC XY: 39965 AN XY: 74262

African (AFR) AF: 0.662 AC: 27420 AN: 41436

American (AMR) AF: 0.537 AC: 8216 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1758 AN: 3470

East Asian (EAS) AF: 0.549 AC: 2832 AN: 5156

South Asian (SAS) AF: 0.426 AC: 2053 AN: 4816

European-Finnish (FIN) AF: 0.425 AC: 4488 AN: 10548

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34391 AN: 67944

Other (OTH) AF: 0.534 AC: 1125 AN: 2108

Alfa AF: 0.524 Hom.: 30277

Bravo AF: 0.564

Asia WGS AF: 0.484 AC: 1681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.090
DANN	Benign	0.52
PhyloP100		-1.8
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: rs9447004; hg19: chr6-74458737;