rs9442947

Variant names:

• chr6-73697254-C-T
• rs9442947
• NM_133493.5:c.75-146C>T

Variant summary

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

The NM_133493.5(CD109):​c.75-146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0472 in 632,298 control chromosomes in the GnomAD database, including 818 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 0.052 (241 hom., cov: 32)
  • Exomes 𝑓: 0.046 (577 hom.)
• Consequence: CD109 NM_133493.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0707 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133493.5. 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
	CD109	NM_133493.5	MANE Select	c.75-146C>T		intron	N/A	NP_598000.2
	CD109	NM_001159587.3		c.75-146C>T		intron	N/A	NP_001153059.1
	CD109	NM_001159588.3		c.75-146C>T		intron	N/A	NP_001153060.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD109	ENST00000287097.6	TSL:1 MANE Select	c.75-146C>T		intron	N/A	ENSP00000287097.4
	CD109	ENST00000437994.6	TSL:1	c.75-146C>T		intron	N/A	ENSP00000388062.2
	CD109	ENST00000422508.6	TSL:1	c.75-146C>T		intron	N/A	ENSP00000404475.2

Frequencies

GnomAD3 genomes AF: 0.0521 AC: 7928 AN: 152108 Hom.: 239 Cov.: 32

Gnomad AFR AF: 0.0725

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0369

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.0740

Gnomad SAS AF: 0.0584

Gnomad FIN AF: 0.0799

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0388

Gnomad OTH AF: 0.0378

GnomAD4 exome AF: 0.0457 AC: 21921 AN: 480072 Hom.: 577 AF XY: 0.0460 AC XY: 11487 AN XY: 249934

African (AFR) AF: 0.0699 AC: 931 AN: 13312

American (AMR) AF: 0.0261 AC: 487 AN: 18660

Ashkenazi Jewish (ASJ) AF: 0.0266 AC: 359 AN: 13510

East Asian (EAS) AF: 0.0788 AC: 2504 AN: 31774

South Asian (SAS) AF: 0.0565 AC: 2371 AN: 41966

European-Finnish (FIN) AF: 0.0756 AC: 3052 AN: 40376

Middle Eastern (MID) AF: 0.0199 AC: 39 AN: 1960

European-Non Finnish (NFE) AF: 0.0377 AC: 10995 AN: 291872

Other (OTH) AF: 0.0444 AC: 1183 AN: 26642

GnomAD4 genome AF: 0.0522 AC: 7951 AN: 152226 Hom.: 241 Cov.: 32 AF XY: 0.0550 AC XY: 4095 AN XY: 74422

African (AFR) AF: 0.0729 AC: 3025 AN: 41506

American (AMR) AF: 0.0368 AC: 564 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3470

East Asian (EAS) AF: 0.0742 AC: 385 AN: 5192

South Asian (SAS) AF: 0.0585 AC: 282 AN: 4824

European-Finnish (FIN) AF: 0.0799 AC: 845 AN: 10578

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0389 AC: 2643 AN: 68026

Other (OTH) AF: 0.0374 AC: 79 AN: 2114

Alfa AF: 0.0403 Hom.: 304

Bravo AF: 0.0489

Asia WGS AF: 0.0730 AC: 255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.1
DANN	Benign	0.63
PhyloP100		-0.0080
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: rs9442947; hg19: chr6-74406977;