Genetic Variant CD109:c.75-146C>T (chr6-73697254-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_133493.5(CD109):c.75-146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0472 in 632,298 control chromosomes in the GnomAD database, including 818 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 0.052 ( 241 hom., cov: 32)

Exomes 𝑓: 0.046 ( 577 hom. )

Consequence

CD109
NM_133493.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00800

Publications

1 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD109	NM_133493.5 link	c.75-146C>T		intron_variant	Intron 1 of 32	ENST00000287097.6	NP_598000.2	Q6YHK3-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CD109	ENST00000287097.6 link	c.75-146C>T	intron_variant	Intron 1 of 32	1	NM_133493.5	ENSP00000287097.4	Q6YHK3-1
CD109	ENST00000437994.6 link	c.75-146C>T	intron_variant	Intron 1 of 32	1		ENSP00000388062.2	Q6YHK3-4
CD109	ENST00000422508.6 link	c.75-146C>T	intron_variant	Intron 1 of 31	1		ENSP00000404475.2	Q6YHK3-2

Frequencies

GnomAD3 genomes

AF:

0.0521

AC:

7928

AN:

152108

Hom.:

239

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0725

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0369

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.0740

Gnomad SAS

AF:

0.0584

Gnomad FIN

AF:

0.0799

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0388

Gnomad OTH

AF:

0.0378

GnomAD4 exome

AF:

0.0457

AC:

21921

AN:

480072

Hom.:

577

AF XY:

0.0460

AC XY:

11487

AN XY:

249934

show subpopulations

African (AFR)

AF:

0.0699

AC:

931

AN:

13312

American (AMR)

AF:

0.0261

AC:

487

AN:

18660

Ashkenazi Jewish (ASJ)

AF:

0.0266

AC:

359

AN:

13510

East Asian (EAS)

AF:

0.0788

AC:

2504

AN:

31774

South Asian (SAS)

AF:

0.0565

AC:

2371

AN:

41966

European-Finnish (FIN)

AF:

0.0756

AC:

3052

AN:

40376

Middle Eastern (MID)

AF:

0.0199

AC:

AN:

1960

European-Non Finnish (NFE)

AF:

0.0377

AC:

10995

AN:

291872

Other (OTH)

AF:

0.0444

AC:

1183

AN:

26642

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

995

1990

2986

3981

4976

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

154

308

462

616

770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0522

AC:

7951

AN:

152226

Hom.:

241

Cov.:

AF XY:

0.0550

AC XY:

4095

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0729

AC:

3025

AN:

41506

American (AMR)

AF:

0.0368

AC:

564

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0285

AC:

AN:

3470

East Asian (EAS)

AF:

0.0742

AC:

385

AN:

5192

South Asian (SAS)

AF:

0.0585

AC:

282

AN:

4824

European-Finnish (FIN)

AF:

0.0799

AC:

845

AN:

10578

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0389

AC:

2643

AN:

68026

Other (OTH)

AF:

0.0374

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

395

790

1185

1580

1975

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0403

Hom.:

304

Bravo

AF:

0.0489

Asia WGS

AF:

0.0730

AC:

255

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.1

(source)

DANN

Benign

0.63

PhyloP100

-0.0080

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over