rs17005845

Positions:

• chr4-140404584-A-G
• chr4-140404584-A-T

Variant summary

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

The NM_004362.3(CLGN):​c.419+1358T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,000 control chromosomes in the GnomAD database, including 2,381 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 0.16 (2381 hom., cov: 32)
• Consequence: CLGN NM_004362.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100

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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLGN	NM_004362.3	c.419+1358T>C		intron_variant		ENST00000325617.10
CLGN	NM_001130675.2	c.419+1358T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLGN	ENST00000325617.10	c.419+1358T>C		intron_variant		1	NM_004362.3	P1
CLGN	ENST00000414773.5	c.419+1358T>C		intron_variant		1		P1
CLGN	ENST00000509477.1	c.419+1358T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24770 AN: 151890 Hom.: 2376 Cov.: 32

Gnomad AFR AF: 0.0672

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.163 AC: 24773 AN: 152000 Hom.: 2381 Cov.: 32 AF XY: 0.169 AC XY: 12538 AN XY: 74288

Gnomad4 AFR AF: 0.0671

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.180

Alfa AF: 0.175 Hom.: 2999

Bravo AF: 0.164

Asia WGS AF: 0.249 AC: 862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.94

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: rs17005845; hg19: chr4-141325738;