Variant chr6-73766068-C-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.1246C>G(p.Gln416Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 1,613,958 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q416H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0037 ( 16 hom. )

Consequence

CD109
NM_133493.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.47

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0073144436).

BP6

Variant 6-73766068-C-G is Benign according to our data. Variant chr6-73766068-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 773471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD109	NM_133493.5 linkuse as main transcript	c.1246C>G	p.Gln416Glu	missense_variant	11/33	ENST00000287097.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD109	ENST00000287097.6 linkuse as main transcript	c.1246C>G	p.Gln416Glu	missense_variant	11/33	1	NM_133493.5	P1	Q6YHK3-1
CD109	ENST00000437994.6 linkuse as main transcript	c.1246C>G	p.Gln416Glu	missense_variant	11/33	1			Q6YHK3-4
CD109	ENST00000422508.6 linkuse as main transcript	c.1015C>G	p.Gln339Glu	missense_variant	10/32	1			Q6YHK3-2
CD109	ENST00000649530.1 linkuse as main transcript	n.1218C>G		non_coding_transcript_exon_variant	10/26

Frequencies

GnomAD3 genomes

AF:

0.00216

AC:

328

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00413

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00220

AC:

552

AN:

251426

Hom.:

AF XY:

0.00216

AC XY:

293

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.00448

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00370

AC:

5415

AN:

1461744

Hom.:

Cov.:

AF XY:

0.00354

AC XY:

2576

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000786

Gnomad4 NFE exome

AF:

0.00471

Gnomad4 OTH exome

AF:

0.00177

GnomAD4 genome

AF:

0.00215

AC:

328

AN:

152214

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

141

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.00413

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00342

Hom.:

Bravo

AF:

0.00226

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00453

AC:

ExAC

AF:

0.00254

AC:

308

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00262

EpiControl

AF:

0.00373

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jun 05, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2022	CD109: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.4

DANN

Benign

0.94

DEOGEN2

Benign

0.0096

.;.;T

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.72

T;T;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.0073

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

2.0

.;M;M

MutationTaster

Benign

0.91

D;D;D

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.99

N;N;N

REVEL

Benign

0.095

Sift

Benign

0.71

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.061

B;B;B

Vest4

0.13

MVP

0.25

MPC

0.032

ClinPred

0.021

GERP RS

3.6

Varity_R

0.090

gMVP

0.36

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