rs9350504

chr6-73748107-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133493.5(CD109):c.634-8536T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 152,166 control chromosomes in the GnomAD database, including 870 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 0.074 (870 hom., cov: 31)
• Consequence: CD109 NM_133493.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07

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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD109	NM_133493.5	c.634-8536T>C		intron_variant		ENST00000287097.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD109	ENST00000287097.6	c.634-8536T>C		intron_variant		1	NM_133493.5	P1
CD109	ENST00000422508.6	c.403-8536T>C		intron_variant		1
CD109	ENST00000437994.6	c.634-8536T>C		intron_variant		1
CD109	ENST00000649530.1	n.606-8536T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0736 AC: 11188 AN: 152046 Hom.: 856 Cov.: 31

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0326

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.0165

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0186

Gnomad OTH AF: 0.0853

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

GnomAD4 genome AF: 0.0738 AC: 11228 AN: 152166 Hom.: 870 Cov.: 31 AF XY: 0.0777 AC XY: 5781 AN XY: 74406

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0326

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.0165

Gnomad4 NFE AF: 0.0186

Gnomad4 OTH AF: 0.0906

Alfa AF: 0.0412 Hom.: 40

Bravo AF: 0.0822

Asia WGS AF: 0.261 AC: 905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.50
Dann	Benign	0.40

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: rs9350504; hg19: chr6-74457830;