rs6755194

Variant names:

• chr2-31220795-T-C
• rs6755194
• NM_001321270.2:c.-444+5733A>G

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+5733A>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 152,104 control chromosomes in the GnomAD database, including 5,172 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 (5172 hom., cov: 33)
• Consequence: CAPN14 NM_001321270.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 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+5733A>G		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+5733A>G		intron	N/A	ENSP00000381805.2

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31236 AN: 151986 Hom.: 5154 Cov.: 33

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0539

Gnomad EAS AF: 0.0574

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.206 AC: 31301 AN: 152104 Hom.: 5172 Cov.: 33 AF XY: 0.204 AC XY: 15160 AN XY: 74362

African (AFR) AF: 0.464 AC: 19230 AN: 41438

American (AMR) AF: 0.141 AC: 2157 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0539 AC: 187 AN: 3472

East Asian (EAS) AF: 0.0574 AC: 297 AN: 5176

South Asian (SAS) AF: 0.140 AC: 676 AN: 4822

European-Finnish (FIN) AF: 0.136 AC: 1436 AN: 10592

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6899 AN: 67998

Other (OTH) AF: 0.168 AC: 354 AN: 2110

Alfa AF: 0.247 Hom.: 2901

Bravo AF: 0.218

Asia WGS AF: 0.134 AC: 467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.89
DANN	Benign	0.57
PhyloP100		-0.23

Splicing

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

Other links and lift over

dbSNP: rs6755194; hg19: chr2-31443661;