rs1370436

Variant names:

• chr6-73814691-G-A
• rs1370436
• NM_133493.5:c.3769-290G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD109	NM_133493.5	c.3769-290G>A		intron_variant	Intron 29 of 32	ENST00000287097.6	NP_598000.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD109	ENST00000287097.6	c.3769-290G>A		intron_variant	Intron 29 of 32	1	NM_133493.5	ENSP00000287097.4
CD109	ENST00000437994.6	c.3718-290G>A		intron_variant	Intron 29 of 32	1		ENSP00000388062.2
CD109	ENST00000422508.6	c.3538-290G>A		intron_variant	Intron 28 of 31	1		ENSP00000404475.2

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

African (AFR) AF: 0.906 AC: 37634 AN: 41538

American (AMR) AF: 0.716 AC: 10931 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2493 AN: 3472

East Asian (EAS) AF: 0.956 AC: 4952 AN: 5178

South Asian (SAS) AF: 0.769 AC: 3700 AN: 4814

European-Finnish (FIN) AF: 0.586 AC: 6193 AN: 10564

Middle Eastern (MID) AF: 0.661 AC: 193 AN: 292

European-Non Finnish (NFE) AF: 0.617 AC: 41941 AN: 67938

Other (OTH) AF: 0.704 AC: 1486 AN: 2112

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
PhyloP100		-0.58
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: rs1370436; hg19: chr6-74524414;