chr11-65183956-G-C

Variant names:

• chr11-65183956-G-C
• rs1467110
• NM_005186.4:c.456+364G>C

Variant summary

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

The NM_005186.4(CAPN1):​c.456+364G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 152,000 control chromosomes in the GnomAD database, including 30,198 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 0.62 (30198 hom., cov: 32)
• Consequence: CAPN1 NM_005186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136
• Publications: 8 publications found

Genes affected

CAPN1 (HGNC:1476): (calpain 1) 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 the large subunit of the ubiquitous enzyme, calpain 1. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

CAPN1 Gene-Disease associations (from GenCC):

• autosomal recessive spastic paraplegia type 76

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPN1	NM_005186.4	c.456+364G>C		intron_variant	Intron 4 of 21	ENST00000279247.11	NP_005177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN1	ENST00000279247.11	c.456+364G>C		intron_variant	Intron 4 of 21	1	NM_005186.4	ENSP00000279247.7

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94572 AN: 151882 Hom.: 30161 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.623 AC: 94664 AN: 152000 Hom.: 30198 Cov.: 32 AF XY: 0.619 AC XY: 45997 AN XY: 74280

African (AFR) AF: 0.495 AC: 20490 AN: 41424

American (AMR) AF: 0.633 AC: 9667 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2105 AN: 3470

East Asian (EAS) AF: 0.467 AC: 2406 AN: 5154

South Asian (SAS) AF: 0.588 AC: 2834 AN: 4822

European-Finnish (FIN) AF: 0.674 AC: 7127 AN: 10570

Middle Eastern (MID) AF: 0.627 AC: 183 AN: 292

European-Non Finnish (NFE) AF: 0.704 AC: 47825 AN: 67966

Other (OTH) AF: 0.641 AC: 1351 AN: 2108

Alfa AF: 0.667 Hom.: 4272

Bravo AF: 0.613

Asia WGS AF: 0.534 AC: 1859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.77
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1467110; hg19: chr11-64951427; COSMIC: COSV107233314; COSMIC: COSV107233314;