NM_004362.3:c.419+1358T>C

Variant names:

• chr4-140404584-A-G
• rs17005845
• NM_004362.3:c.419+1358T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CLGN	NM_004362.3	c.419+1358T>C		intron_variant	Intron 5 of 14	ENST00000325617.10	NP_004353.1
CLGN	NM_001130675.2	c.419+1358T>C		intron_variant	Intron 6 of 15		NP_001124147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLGN	ENST00000325617.10	c.419+1358T>C		intron_variant	Intron 5 of 14	1	NM_004362.3	ENSP00000326699.5
CLGN	ENST00000414773.5	c.419+1358T>C		intron_variant	Intron 6 of 15	1		ENSP00000392782.1
CLGN	ENST00000509477.1	c.419+1358T>C		intron_variant	Intron 6 of 7	3		ENSP00000424593.1

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

African (AFR) AF: 0.0671 AC: 2785 AN: 41490

American (AMR) AF: 0.271 AC: 4134 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 617 AN: 3468

East Asian (EAS) AF: 0.287 AC: 1485 AN: 5170

South Asian (SAS) AF: 0.262 AC: 1261 AN: 4816

European-Finnish (FIN) AF: 0.200 AC: 2113 AN: 10546

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.173 AC: 11752 AN: 67936

Other (OTH) AF: 0.180 AC: 379 AN: 2104

Alfa AF: 0.175 Hom.: 3403

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
PhyloP100		-0.0010
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17005845; hg19: chr4-141325738;