4-140427103-A-C

Position:

• chr4-140427103-A-C

Variant summary

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

The ENST00000325617.10(CLGN):​c.-10+434T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 151,996 control chromosomes in the GnomAD database, including 63,074 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 0.91 (63074 hom., cov: 32)
• Consequence: CLGN ENST00000325617.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358

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 (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLGN	NM_004362.3	c.-10+434T>G		intron_variant		ENST00000325617.10	NP_004353.1
CLGN	NM_001130675.2	c.-93-316T>G		intron_variant			NP_001124147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLGN	ENST00000325617.10	c.-10+434T>G		intron_variant		1	NM_004362.3	ENSP00000326699	P1
CLGN	ENST00000414773.5	c.-93-316T>G		intron_variant		1		ENSP00000392782	P1
CLGN	ENST00000509477.1	c.-93-316T>G		intron_variant		3		ENSP00000424593

Frequencies

GnomAD3 genomes AF: 0.908 AC: 137968 AN: 151878 Hom.: 63043 Cov.: 32

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.971

Gnomad MID AF: 0.888

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.922

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.908 AC: 138047 AN: 151996 Hom.: 63074 Cov.: 32 AF XY: 0.908 AC XY: 67501 AN XY: 74322

Gnomad4 AFR AF: 0.797

Gnomad4 AMR AF: 0.930

Gnomad4 ASJ AF: 0.893

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.900

Gnomad4 FIN AF: 0.971

Gnomad4 NFE AF: 0.955

Gnomad4 OTH AF: 0.923

Alfa AF: 0.941 Hom.: 17560

Bravo AF: 0.903

Asia WGS AF: 0.939 AC: 3265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.1
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs11945012; hg19: chr4-141348257;