19-38767470-C-T

Variant names:

• chr19-38767470-C-T
• rs7248584
• ENST00000601953.5:c.-141+2328G>A

Variant summary

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

The ENST00000601953.5(CAPN12):​c.-141+2328G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 151,874 control chromosomes in the GnomAD database, including 13,025 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 0.41 (13025 hom., cov: 31)
• Consequence: CAPN12 ENST00000601953.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.26
• Publications: 8 publications found

Genes affected

CAPN12 (HGNC:13249): (calpain 12) 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]

CAPN12 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AR Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN12	ENST00000601953.5	c.-141+2328G>A		intron_variant	Intron 1 of 19	5		ENSP00000473156.1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61773 AN: 151756 Hom.: 13012 Cov.: 31

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.407 AC: 61802 AN: 151874 Hom.: 13025 Cov.: 31 AF XY: 0.404 AC XY: 30027 AN XY: 74238

African (AFR) AF: 0.354 AC: 14665 AN: 41428

American (AMR) AF: 0.333 AC: 5057 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1487 AN: 3462

East Asian (EAS) AF: 0.157 AC: 808 AN: 5148

South Asian (SAS) AF: 0.357 AC: 1716 AN: 4812

European-Finnish (FIN) AF: 0.476 AC: 5027 AN: 10552

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.465 AC: 31623 AN: 67948

Other (OTH) AF: 0.398 AC: 840 AN: 2110

Alfa AF: 0.434 Hom.: 55141

Bravo AF: 0.391

Asia WGS AF: 0.244 AC: 849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.54
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7248584; hg19: chr19-39258110;