rs13386850

Positions:

• chr2-31222825-A-C

Variant summary

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

The NM_001321270.2(CAPN14):​c.-444+3703T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,108 control chromosomes in the GnomAD database, including 5,184 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 0.21 (5184 hom., cov: 32)
• Consequence: CAPN14 NM_001321270.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAPN14	NM_001321270.2	c.-444+3703T>G		intron_variant
CAPN14	XM_011532864.4	c.-53+3703T>G		intron_variant
CAPN14	XM_011532865.2	c.-53+3703T>G		intron_variant
CAPN14	XM_047444407.1	c.-53+3703T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAPN14	ENST00000398824.6	c.-53+3703T>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31271 AN: 151992 Hom.: 5164 Cov.: 32

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.0554

Gnomad EAS AF: 0.0565

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.206 AC: 31338 AN: 152108 Hom.: 5184 Cov.: 32 AF XY: 0.204 AC XY: 15170 AN XY: 74380

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.0554

Gnomad4 EAS AF: 0.0562

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.168

Alfa AF: 0.113 Hom.: 1848

Bravo AF: 0.218

Asia WGS AF: 0.134 AC: 467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.8
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13386850; hg19: chr2-31445691;