rs2368524

Variant names:

• chr19-38761598-G-A
• rs2368524
• ENST00000601953.5:c.-141+8200C>T

Variant summary

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

The ENST00000601953.5(CAPN12):​c.-141+8200C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 151,930 control chromosomes in the GnomAD database, including 967 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 0.11 (967 hom., cov: 32)
• Consequence: CAPN12 ENST00000601953.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 9 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000601953.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN12	ENST00000601953.5	TSL:5	c.-141+8200C>T		intron	N/A	ENSP00000473156.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16080 AN: 151812 Hom.: 969 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0807

Gnomad EAS AF: 0.0435

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0664

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0867

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.106 AC: 16102 AN: 151930 Hom.: 967 Cov.: 32 AF XY: 0.106 AC XY: 7888 AN XY: 74254

African (AFR) AF: 0.149 AC: 6171 AN: 41428

American (AMR) AF: 0.128 AC: 1950 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.0807 AC: 280 AN: 3468

East Asian (EAS) AF: 0.0436 AC: 226 AN: 5184

South Asian (SAS) AF: 0.129 AC: 622 AN: 4816

European-Finnish (FIN) AF: 0.0664 AC: 699 AN: 10530

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0867 AC: 5895 AN: 67964

Other (OTH) AF: 0.103 AC: 217 AN: 2108

Alfa AF: 0.0909 Hom.: 519

Bravo AF: 0.115

Asia WGS AF: 0.109 AC: 381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.52
PhyloP100		-1.9
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: rs2368524; hg19: chr19-39252238;