rs2567241

chr4-140402008-C-A

Variant summary

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

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. 12/19 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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.059 (304 hom., cov: 33)
  • Exomes 𝑓: 0.045 (1850 hom.)
• Consequence: CLGN NM_004362.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.73

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]

ACMG classification

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	UniProt
CLGN	NM_004362.3	c.478G>T	p.Ala160Ser	missense_variant	6/15	ENST00000325617.10
CLGN	NM_001130675.2	c.478G>T	p.Ala160Ser	missense_variant	7/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLGN	ENST00000325617.10	c.478G>T	p.Ala160Ser	missense_variant	6/15	1	NM_004362.3	P1
CLGN	ENST00000414773.5	c.478G>T	p.Ala160Ser	missense_variant	7/16	1		P1
CLGN	ENST00000509477.1	c.478G>T	p.Ala160Ser	missense_variant	7/8	3

Frequencies

GnomAD3 genomes AF: 0.0591 AC: 8967 AN: 151822 Hom.: 304 Cov.: 33

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

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.: 25 AF XY: 0.0464 AC XY: 32822 AN XY: 706944

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.: 33 AF XY: 0.0602 AC XY: 4473 AN XY: 74250

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	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	14
Dann	Benign	0.61
DEOGEN2	Benign	0.035	T;T;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.92	D;.;D
MetaRNN	Benign	0.0026	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-3.1	N;N;.
MutationTaster	Benign	0.0092	P;P;P
PrimateAI	Benign	0.35	T
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	T
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

Other links and lift over

dbSNP: rs2567241; hg19: chr4-141323162; COSMIC: COSV57774375;