NM_001321270.2:c.-444+3779T>C

Variant names:

• chr2-31222749-A-G
• rs13386745
• NM_001321270.2:c.-444+3779T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321270.2(CAPN14):​c.-444+3779T>C 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 152,024 control chromosomes in the GnomAD database, including 2,616 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 (2616 hom., cov: 32)
• Consequence: CAPN14 NM_001321270.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.364
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321270.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN14	NM_001321270.2		c.-444+3779T>C		intron	N/A	NP_001308199.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN14	ENST00000398824.6	TSL:2	n.-53+3779T>C		intron	N/A	ENSP00000381805.2

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24315 AN: 151906 Hom.: 2602 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0539

Gnomad EAS AF: 0.0564

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.160 AC: 24374 AN: 152024 Hom.: 2616 Cov.: 32 AF XY: 0.160 AC XY: 11878 AN XY: 74336

African (AFR) AF: 0.306 AC: 12680 AN: 41404

American (AMR) AF: 0.124 AC: 1888 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0539 AC: 187 AN: 3468

East Asian (EAS) AF: 0.0563 AC: 292 AN: 5184

South Asian (SAS) AF: 0.139 AC: 670 AN: 4812

European-Finnish (FIN) AF: 0.136 AC: 1435 AN: 10580

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6875 AN: 67994

Other (OTH) AF: 0.136 AC: 286 AN: 2110

Alfa AF: 0.115 Hom.: 940

Bravo AF: 0.165

Asia WGS AF: 0.126 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.57
PhyloP100		0.36

Splicing

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

Other links and lift over

dbSNP: rs13386745; hg19: chr2-31445615;