chr1-223612249-C-T

Position:

• chr1-223612249-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001143962.2(CAPN8):​c.1320G>A​(p.Lys440Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000531 in 1,234,276 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00021 (2 hom.)
• Consequence: CAPN8 NM_001143962.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13

Genes affected

CAPN8 (HGNC:1485): (calpain 8) Predicted to enable calcium-dependent cysteine-type endopeptidase activity and identical protein binding activity. Predicted to be involved in proteolysis. Predicted to act upstream of or within calcium-dependent self proteolysis. Predicted to be located in Golgi apparatus. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 1-223612249-C-T is Benign according to our data. Variant chr1-223612249-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2639919.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.13 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPN8	NM_001143962.2	c.1320G>A	p.Lys440Lys	synonymous_variant	11/21	ENST00000366872.10	NP_001137434.1
CAPN8	XM_017001265.2	c.837G>A	p.Lys279Lys	synonymous_variant	8/18		XP_016856754.1
CAPN8	XM_017001266.2	c.639G>A	p.Lys213Lys	synonymous_variant	6/16		XP_016856755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPN8	ENST00000366872.10	c.1320G>A	p.Lys440Lys	synonymous_variant	11/21	1	NM_001143962.2	ENSP00000355837.6

Frequencies

GnomAD3 genomes AF: 0.00281 AC: 427 AN: 152170 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00967

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.000211 AC: 228 AN: 1081988 Hom.: 2 Cov.: 30 AF XY: 0.000176 AC XY: 90 AN XY: 510840

Gnomad4 AFR exome AF: 0.00838

Gnomad4 AMR exome AF: 0.00107

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000377

Gnomad4 SAS exome AF: 0.0000511

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000217

Gnomad4 OTH exome AF: 0.000502

GnomAD4 genome AF: 0.00280 AC: 427 AN: 152288 Hom.: 1 Cov.: 31 AF XY: 0.00274 AC XY: 204 AN XY: 74474

Gnomad4 AFR AF: 0.00964

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00146 Hom.: 0

Bravo AF: 0.00312

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

CAPN8: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.1
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs552094413; hg19: chr1-223799951;