19-38761598-G-A

Position:

• chr19-38761598-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAPN12	ENST00000601953.5	c.-141+8200C>T		intron_variant		5

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

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.0807

Gnomad4 EAS AF: 0.0436

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0664

Gnomad4 NFE AF: 0.0867

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0906 Hom.: 246

Bravo AF: 0.115

Asia WGS AF: 0.109 AC: 381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2368524; hg19: chr19-39252238;