11-65182905-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_005186.4(CAPN1):c.204G>C(p.Leu68=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,610,132 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (15 hom.)
• Consequence: CAPN1 NM_005186.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 11-65182905-G-C is Benign according to our data. Variant chr11-65182905-G-C is described in ClinVar as [Benign]. Clinvar id is 781962.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.13 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00108 (164/152296) while in subpopulation SAS AF= 0.00994 (48/4830). AF 95% confidence interval is 0.0077. There are 2 homozygotes in gnomad4. There are 87 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAPN1	NM_005186.4	c.204G>C	p.Leu68=	synonymous_variant	2/22	ENST00000279247.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAPN1	ENST00000279247.11	c.204G>C	p.Leu68=	synonymous_variant	2/22	1	NM_005186.4	P1

Frequencies

GnomAD3 genomes AF: 0.00108 AC: 164 AN: 152178 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00993

Gnomad FIN AF: 0.00367

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00259 AC: 624 AN: 240732 Hom.: 4 AF XY: 0.00306 AC XY: 400 AN XY: 130664

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000119

Gnomad ASJ exome AF: 0.0139

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0115

Gnomad FIN exome AF: 0.00260

Gnomad NFE exome AF: 0.000680

Gnomad OTH exome AF: 0.00204

GnomAD4 exome AF: 0.00138 AC: 2015 AN: 1457836 Hom.: 15 Cov.: 31 AF XY: 0.00175 AC XY: 1269 AN XY: 724884

Gnomad4 AFR exome AF: 0.0000899

Gnomad4 AMR exome AF: 0.000136

Gnomad4 ASJ exome AF: 0.0125

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0115

Gnomad4 FIN exome AF: 0.00316

Gnomad4 NFE exome AF: 0.000338

Gnomad4 OTH exome AF: 0.00229

GnomAD4 genome AF: 0.00108 AC: 164 AN: 152296 Hom.: 2 Cov.: 33 AF XY: 0.00117 AC XY: 87 AN XY: 74470

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00994

Gnomad4 FIN AF: 0.00367

Gnomad4 NFE AF: 0.000470

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00201 Hom.: 0

Bravo AF: 0.000733

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 09, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	7.7
Dann	Benign	0.57

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: rs17881440; hg19: chr11-64950376;