rs9442947

Positions:

• chr6-73697254-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD109	NM_133493.5	c.75-146C>T		intron_variant		ENST00000287097.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD109	ENST00000287097.6	c.75-146C>T		intron_variant		1	NM_133493.5	P1
CD109	ENST00000422508.6	c.75-146C>T		intron_variant		1
CD109	ENST00000437994.6	c.75-146C>T		intron_variant		1

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

Gnomad4 AFR exome AF: 0.0699

Gnomad4 AMR exome AF: 0.0261

Gnomad4 ASJ exome AF: 0.0266

Gnomad4 EAS exome AF: 0.0788

Gnomad4 SAS exome AF: 0.0565

Gnomad4 FIN exome AF: 0.0756

Gnomad4 NFE exome AF: 0.0377

Gnomad4 OTH exome AF: 0.0444

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

Gnomad4 AFR AF: 0.0729

Gnomad4 AMR AF: 0.0368

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.0742

Gnomad4 SAS AF: 0.0585

Gnomad4 FIN AF: 0.0799

Gnomad4 NFE AF: 0.0389

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0387 Hom.: 185

Bravo AF: 0.0489

Asia WGS AF: 0.0730 AC: 255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.1
DANN	Benign	0.63

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: rs9442947; hg19: chr6-74406977;