chr6-73814691-G-A

Position:

• chr6-73814691-G-A

Variant summary

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

The NM_133493.5(CD109):​c.3769-290G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 152,076 control chromosomes in the GnomAD database, including 41,292 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 0.72 (41292 hom., cov: 32)
• Consequence: CD109 NM_133493.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.577

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD109	NM_133493.5	c.3769-290G>A		intron_variant		ENST00000287097.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD109	ENST00000287097.6	c.3769-290G>A		intron_variant		1	NM_133493.5	P1
CD109	ENST00000422508.6	c.3538-290G>A		intron_variant		1
CD109	ENST00000437994.6	c.3718-290G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109896 AN: 151960 Hom.: 41229 Cov.: 32

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.723 AC: 110017 AN: 152076 Hom.: 41292 Cov.: 32 AF XY: 0.723 AC XY: 53769 AN XY: 74318

Gnomad4 AFR AF: 0.906

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.718

Gnomad4 EAS AF: 0.956

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.704

Alfa AF: 0.676 Hom.: 4425

Bravo AF: 0.743

Asia WGS AF: 0.839 AC: 2916 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	0.48
DANN	Benign	0.38

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: rs1370436; hg19: chr6-74524414;