Variant chr6-73736491-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_133493.5(CD109):c.616A>G(p.Ile206Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,612,012 control chromosomes in the GnomAD database, including 111 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 4 hom., cov: 32)

Exomes 𝑓: 0.011 ( 107 hom. )

Consequence

CD109
NM_133493.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.98

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:

CD109 (HGNC:):

CD109 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008697569).

BP6

Variant 6-73736491-A-G is Benign according to our data. Variant chr6-73736491-A-G is described in ClinVar as [Benign]. Clinvar id is 776594.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD109	NM_133493.5 linkuse as main transcript	c.616A>G	p.Ile206Val	missense_variant	5/33	ENST00000287097.6	NP_598000.2	Q6YHK3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CD109	ENST00000287097.6 linkuse as main transcript	c.616A>G	p.Ile206Val	missense_variant	5/33	1	NM_133493.5	ENSP00000287097.4	Q6YHK3-1
CD109	ENST00000437994.6 linkuse as main transcript	c.616A>G	p.Ile206Val	missense_variant	5/33	1		ENSP00000388062.2	Q6YHK3-4
CD109	ENST00000422508.6 linkuse as main transcript	c.385A>G	p.Ile129Val	missense_variant	4/32	1		ENSP00000404475.2	Q6YHK3-2
CD109	ENST00000649530.1 linkuse as main transcript	n.588A>G		non_coding_transcript_exon_variant	4/26

Frequencies

GnomAD3 genomes

AF:

0.00759

AC:

1155

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00438

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00911

Gnomad FIN

AF:

0.0146

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0115

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00907

AC:

2262

AN:

249306

Hom.:

AF XY:

0.00949

AC XY:

1280

AN XY:

134858

show subpopulations

Gnomad AFR exome

AF:

0.00137

Gnomad AMR exome

AF:

0.00250

Gnomad ASJ exome

AF:

0.00449

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0109

Gnomad FIN exome

AF:

0.0172

Gnomad NFE exome

AF:

0.0120

Gnomad OTH exome

AF:

0.00940

GnomAD4 exome

AF:

0.0106

AC:

15405

AN:

1459670

Hom.:

107

Cov.:

AF XY:

0.0106

AC XY:

7697

AN XY:

726220

show subpopulations

Gnomad4 AFR exome

AF:

0.000989

Gnomad4 AMR exome

AF:

0.00278

Gnomad4 ASJ exome

AF:

0.00525

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0109

Gnomad4 FIN exome

AF:

0.0168

Gnomad4 NFE exome

AF:

0.0114

Gnomad4 OTH exome

AF:

0.00959

GnomAD4 genome

AF:

0.00756

AC:

1152

AN:

152342

Hom.:

Cov.:

AF XY:

0.00768

AC XY:

572

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00161

Gnomad4 AMR

AF:

0.00438

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00850

Gnomad4 FIN

AF:

0.0146

Gnomad4 NFE

AF:

0.0115

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.0101

Hom.:

Bravo

AF:

0.00646

TwinsUK

AF:

0.0108

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.0133

AC:

114

ExAC

AF:

0.00983

AC:

1194

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.0102

EpiControl

AF:

0.0104

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	CD109: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 05, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

.;.;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.77

T;T;T

MetaRNN

Benign

0.0087

T;T;T

MetaSVM

Benign

-0.48

MutationAssessor

Benign

1.7

.;L;L

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.83

N;N;N

REVEL

Benign

0.24

Sift

Uncertain

0.010

D;D;D

Sift4G

Uncertain

0.034

D;D;D

Polyphen

0.98

D;B;P

Vest4

0.33

MVP

0.67

MPC

0.097

ClinPred

0.013

GERP RS

4.7

Varity_R

0.073

gMVP

0.43

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over