11-65204160-G-C

Variant names:

• chr11-65204160-G-C
• rs678343
• NM_005186.4:c.1166-523G>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.1166-523G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,080 control chromosomes in the GnomAD database, including 41,672 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 (41672 hom., cov: 31)
• Consequence: CAPN1 NM_005186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005186.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN1	NM_005186.4	MANE Select	c.1166-523G>C		intron	N/A	NP_005177.2
	CAPN1	NM_001198868.2		c.1166-523G>C		intron	N/A	NP_001185797.1	P07384
	CAPN1	NM_001198869.2		c.1166-523G>C		intron	N/A	NP_001185798.1	P07384

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN1	ENST00000279247.11	TSL:1 MANE Select	c.1166-523G>C		intron	N/A	ENSP00000279247.7	P07384
	CAPN1	ENST00000524773.5	TSL:1	c.1166-523G>C		intron	N/A	ENSP00000434176.1	P07384
	CAPN1	ENST00000527323.5	TSL:1	c.1166-523G>C		intron	N/A	ENSP00000431984.1	P07384

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111350 AN: 151962 Hom.: 41651 Cov.: 31

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.760

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

GnomAD4 genome AF: 0.733 AC: 111424 AN: 152080 Hom.: 41672 Cov.: 31 AF XY: 0.728 AC XY: 54130 AN XY: 74326

African (AFR) AF: 0.579 AC: 24009 AN: 41458

American (AMR) AF: 0.737 AC: 11255 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2544 AN: 3470

East Asian (EAS) AF: 0.663 AC: 3421 AN: 5160

South Asian (SAS) AF: 0.692 AC: 3329 AN: 4812

European-Finnish (FIN) AF: 0.761 AC: 8059 AN: 10586

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.825 AC: 56125 AN: 68008

Other (OTH) AF: 0.762 AC: 1610 AN: 2112

Alfa AF: 0.780 Hom.: 5821

Bravo AF: 0.726

Asia WGS AF: 0.684 AC: 2382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.5
DANN	Benign	0.58
PhyloP100		-0.73
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: rs678343; hg19: chr11-64971631;