2-30783858-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144575.3(CAPN13):c.198+3270G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,120 control chromosomes in the GnomAD database, including 41,036 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 0.73 (41036 hom., cov: 32)
• Consequence: CAPN13 NM_144575.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.626

Genes affected

CAPN13 (HGNC:16663): (calpain 13) 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAPN13	NM_144575.3	c.198+3270G>C		intron_variant		ENST00000295055.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAPN13	ENST00000295055.12	c.198+3270G>C		intron_variant		5	NM_144575.3	P1
CAPN13	ENST00000458085.6	c.198+3270G>C		intron_variant, NMD_transcript_variant		5
CAPN13	ENST00000485248.2	c.198+3270G>C		intron_variant, NMD_transcript_variant		3
CAPN13	ENST00000465960.2	n.547+3270G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110979 AN: 152002 Hom.: 41010 Cov.: 32

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.715

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

GnomAD4 genome AF: 0.730 AC: 111060 AN: 152120 Hom.: 41036 Cov.: 32 AF XY: 0.733 AC XY: 54485 AN XY: 74342

Gnomad4 AFR AF: 0.833

Gnomad4 AMR AF: 0.772

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.746

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.713

Alfa AF: 0.593 Hom.: 1597

Bravo AF: 0.745

Asia WGS AF: 0.728 AC: 2532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	6.3
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6548036; hg19: chr2-31006724;