rs13408922

Positions:

• chr2-31221960-C-A
• chr2-31221960-C-T

Variant summary

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

The NM_001321270.2(CAPN14):​c.-444+4568G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,142 control chromosomes in the GnomAD database, including 2,607 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 (2607 hom., cov: 32)
• Consequence: CAPN14 NM_001321270.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341

Genes affected

CAPN14 (HGNC:16664): (calpain 14) Calpains are a family of cytosolic calcium-activated cysteine proteases involved in a variety of cellular processes including apoptosis, cell division, modulation of integrin-cytoskeletal interactions, and synaptic plasticity (Dear et al., 2000 [PubMed 10964513]). CAPN14 belongs to the calpain large subunit family.[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPN14	NM_001321270.2	c.-444+4568G>T		intron_variant			NP_001308199.1
CAPN14	XM_011532864.4	c.-53+4568G>T		intron_variant			XP_011531166.1
CAPN14	XM_011532865.2	c.-53+4568G>T		intron_variant			XP_011531167.1
CAPN14	XM_047444407.1	c.-53+4568G>T		intron_variant			XP_047300363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPN14	ENST00000398824.6	n.-53+4568G>T		intron_variant		2		ENSP00000381805.2

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24270 AN: 152024 Hom.: 2595 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0539

Gnomad EAS AF: 0.0565

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.160 AC: 24327 AN: 152142 Hom.: 2607 Cov.: 32 AF XY: 0.159 AC XY: 11856 AN XY: 74368

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.0539

Gnomad4 EAS AF: 0.0565

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.134

Alfa AF: 0.105 Hom.: 1315

Bravo AF: 0.165

Asia WGS AF: 0.125 AC: 436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.55
DANN	Benign	0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13408922; hg19: chr2-31444826;