rs17010141

Positions:

• chr2-30751709-A-C

Variant summary

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

The NM_144575.3(CAPN13):​c.1088-458T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0845 in 152,264 control chromosomes in the GnomAD database, including 830 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 0.084 (830 hom., cov: 33)
• Consequence: CAPN13 NM_144575.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.520

Genes affected

CAPN13 (HGNC:16663): (calpain 13) The calpains, calcium-activated neutral proteases, are nonlysosomal, intracellular cysteine proteases. The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. The ubiquitous enzymes consist of heterodimers with distinct large, catalytic subunits associated with a common small, regulatory subunit. This gene encodes a member of the calpain large subunit family. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPN13	NM_144575.3	c.1088-458T>G		intron_variant		ENST00000295055.12	NP_653176.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPN13	ENST00000295055.12	c.1088-458T>G		intron_variant		5	NM_144575.3	ENSP00000295055	P1
CAPN13	ENST00000458085.6	c.1088-458T>G		intron_variant, NMD_transcript_variant		5		ENSP00000416191

Frequencies

GnomAD3 genomes AF: 0.0845 AC: 12858 AN: 152146 Hom.: 833 Cov.: 33

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0839

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0831

Gnomad OTH AF: 0.0946

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

GnomAD4 genome AF: 0.0845 AC: 12859 AN: 152264 Hom.: 830 Cov.: 33 AF XY: 0.0888 AC XY: 6610 AN XY: 74448

Gnomad4 AFR AF: 0.0197

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.0839

Gnomad4 NFE AF: 0.0832

Gnomad4 OTH AF: 0.0931

Alfa AF: 0.0890 Hom.: 1398

Bravo AF: 0.0889

Asia WGS AF: 0.194 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.9
DANN	Benign	0.66

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: rs17010141; hg19: chr2-30974575;