rs10455097

Positions:

• chr6-73783709-A-C

Variant summary

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

The NM_133493.5(CD109):​c.2108A>C​(p.Tyr703Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 1,573,170 control chromosomes in the GnomAD database, including 209,847 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.54 (22741 hom., cov: 32)
  • Exomes 𝑓: 0.51 (187106 hom.)
• Consequence: CD109 NM_133493.5 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17

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]

CD109 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.0415844E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD109	NM_133493.5	c.2108A>C	p.Tyr703Ser	missense_variant, splice_region_variant	19/33	ENST00000287097.6	NP_598000.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD109	ENST00000287097.6	c.2108A>C	p.Tyr703Ser	missense_variant, splice_region_variant	19/33	1	NM_133493.5	ENSP00000287097.4
CD109	ENST00000437994.6	c.2108A>C	p.Tyr703Ser	missense_variant, splice_region_variant	19/33	1		ENSP00000388062.2
CD109	ENST00000422508.6	c.1877A>C	p.Tyr626Ser	missense_variant, splice_region_variant	18/32	1		ENSP00000404475.2
CD109	ENST00000649530.1	n.2080A>C		splice_region_variant, non_coding_transcript_exon_variant	18/26

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82155 AN: 151846 Hom.: 22719 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.531

GnomAD3 exomes AF: 0.512 AC: 127834 AN: 249794 Hom.: 33388 AF XY: 0.502 AC XY: 67764 AN XY: 134990

Gnomad AFR exome AF: 0.649

Gnomad AMR exome AF: 0.600

Gnomad ASJ exome AF: 0.523

Gnomad EAS exome AF: 0.518

Gnomad SAS exome AF: 0.418

Gnomad FIN exome AF: 0.431

Gnomad NFE exome AF: 0.504

Gnomad OTH exome AF: 0.509

GnomAD4 exome AF: 0.511 AC: 725611 AN: 1421206 Hom.: 187106 Cov.: 24 AF XY: 0.508 AC XY: 360195 AN XY: 709484

Gnomad4 AFR exome AF: 0.653

Gnomad4 AMR exome AF: 0.592

Gnomad4 ASJ exome AF: 0.524

Gnomad4 EAS exome AF: 0.517

Gnomad4 SAS exome AF: 0.424

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.513

Gnomad4 OTH exome AF: 0.517

GnomAD4 genome AF: 0.541 AC: 82220 AN: 151964 Hom.: 22741 Cov.: 32 AF XY: 0.534 AC XY: 39706 AN XY: 74300

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.525

Alfa AF: 0.511 Hom.: 49400

Bravo AF: 0.560

TwinsUK AF: 0.514 AC: 1905

ALSPAC AF: 0.514 AC: 1982

ESP6500AA AF: 0.645 AC: 2841

ESP6500EA AF: 0.511 AC: 4395

ExAC AF: 0.509 AC: 61792

Asia WGS AF: 0.469 AC: 1629 AN: 3478

EpiCase AF: 0.513

EpiControl AF: 0.508

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.034
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	17
DANN	Benign	0.45
DEOGEN2	Benign	0.0029	.;.;T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.32	T;T;T
MetaRNN	Benign	0.0000040	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.8	.;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	1.9	N;N;N
REVEL	Benign	0.11
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.44	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.074
MPC		0.038
ClinPred		0.0030	T
GERP RS		5.2
Varity_R		0.063
gMVP		0.37

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: rs10455097; hg19: chr6-74493432; COSMIC: COSV54646336;