6-73730412-A-G

Variant names:

• chr6-73730412-A-G
• rs1421308224
• NM_133493.5:c.345A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_133493.5(CD109):​c.345A>G​(p.Leu115Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CD109 NM_133493.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=-0.156 with no splicing effect.

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.345A>G	p.Leu115Leu	synonymous	Exon 4 of 33	NP_598000.2	Q6YHK3-1
	CD109	NM_001159587.3		c.345A>G	p.Leu115Leu	synonymous	Exon 4 of 33	NP_001153059.1	Q6YHK3-4
	CD109	NM_001159588.3		c.277-5971A>G		intron	N/A	NP_001153060.1	Q6YHK3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD109	ENST00000287097.6	TSL:1 MANE Select	c.345A>G	p.Leu115Leu	synonymous	Exon 4 of 33	ENSP00000287097.4	Q6YHK3-1
	CD109	ENST00000437994.6	TSL:1	c.345A>G	p.Leu115Leu	synonymous	Exon 4 of 33	ENSP00000388062.2	Q6YHK3-4
	CD109	ENST00000422508.6	TSL:1	c.277-5971A>G		intron	N/A	ENSP00000404475.2	Q6YHK3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251332 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.8
DANN	Benign	0.66
PhyloP100		-0.16

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: rs1421308224; hg19: chr6-74440135;