Variant rs2567241 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004362.3(CLGN):c.478G>T(p.Ala160Ser) variant causes a missense change. The variant allele was found at a frequency of 0.046 in 1,571,392 control chromosomes in the GnomAD database, including 2,154 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.059 ( 304 hom., cov: 33)

Exomes 𝑓: 0.045 ( 1850 hom. )

Consequence

CLGN
NM_004362.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.73

Variant links:

Genes affected

CLGN (HGNC:2060): (calmegin) Calmegin is a testis-specific endoplasmic reticulum chaperone protein. CLGN may play a role in spermatogeneisis and infertility. [provided by RefSeq, Jul 2008]

CLGN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025804043).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLGN	NM_004362.3 link	c.478G>T	p.Ala160Ser	missense_variant	6/15	ENST00000325617.10	NP_004353.1	O14967-1A0A140VKG2
CLGN	NM_001130675.2 link	c.478G>T	p.Ala160Ser	missense_variant	7/16		NP_001124147.1	O14967-1A0A140VKG2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CLGN	ENST00000325617.10 link	c.478G>T	p.Ala160Ser	missense_variant	6/15	1	NM_004362.3	ENSP00000326699.5	O14967-1
CLGN	ENST00000414773.5 link	c.478G>T	p.Ala160Ser	missense_variant	7/16	1		ENSP00000392782.1	O14967-1
CLGN	ENST00000509477.1 link	c.478G>T	p.Ala160Ser	missense_variant	7/8	3		ENSP00000424593.1	D6RAZ4

Frequencies

GnomAD3 genomes

AF:

0.0591

AC:

8967

AN:

151822

Hom.:

304

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0918

Gnomad AMI

AF:

0.0648

Gnomad AMR

AF:

0.0547

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.00539

Gnomad SAS

AF:

0.0964

Gnomad FIN

AF:

0.0290

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0435

Gnomad OTH

AF:

0.0584

GnomAD3 exomes

AF:

0.0523

AC:

12196

AN:

233190

Hom.:

460

AF XY:

0.0537

AC XY:

6788

AN XY:

126382

show subpopulations

Gnomad AFR exome

AF:

0.0858

Gnomad AMR exome

AF:

0.0610

Gnomad ASJ exome

AF:

0.0962

Gnomad EAS exome

AF:

0.00471

Gnomad SAS exome

AF:

0.0955

Gnomad FIN exome

AF:

0.0256

Gnomad NFE exome

AF:

0.0434

Gnomad OTH exome

AF:

0.0540

GnomAD4 exome

AF:

0.0446

AC:

63359

AN:

1419452

Hom.:

1850

Cov.:

AF XY:

0.0464

AC XY:

32822

AN XY:

706944

show subpopulations

Gnomad4 AFR exome

AF:

0.0839

Gnomad4 AMR exome

AF:

0.0620

Gnomad4 ASJ exome

AF:

0.0983

Gnomad4 EAS exome

AF:

0.00580

Gnomad4 SAS exome

AF:

0.0989

Gnomad4 FIN exome

AF:

0.0260

Gnomad4 NFE exome

AF:

0.0392

Gnomad4 OTH exome

AF:

0.0516

GnomAD4 genome

AF:

0.0591

AC:

8974

AN:

151940

Hom.:

304

Cov.:

AF XY:

0.0602

AC XY:

4473

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.0920

Gnomad4 AMR

AF:

0.0547

Gnomad4 ASJ

AF:

0.107

Gnomad4 EAS

AF:

0.00540

Gnomad4 SAS

AF:

0.0948

Gnomad4 FIN

AF:

0.0290

Gnomad4 NFE

AF:

0.0435

Gnomad4 OTH

AF:

0.0573

Alfa

AF:

0.0490

Hom.:

470

Bravo

AF:

0.0612

TwinsUK

AF:

0.0413

AC:

153

ALSPAC

AF:

0.0402

AC:

155

ESP6500AA

AF:

0.0872

AC:

384

ESP6500EA

AF:

0.0473

AC:

405

ExAC

AF:

0.0572

AC:

6940

Asia WGS

AF:

0.0450

AC:

155

AN:

3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.61

DEOGEN2

Benign

0.035

T;T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.92

D;.;D

MetaRNN

Benign

0.0026

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-3.1

N;N;.

PrimateAI

Benign

0.35

PROVEAN

Benign

1.2

N;N;N

REVEL

Benign

0.097

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;.

Polyphen

0.0030

B;B;.

Vest4

0.040

MPC

0.088

ClinPred

0.015

GERP RS

4.6

Varity_R

0.099

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over