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GeneBe

1-223712784-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001748.5(CAPN2):c.144C>T(p.Asp48=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,578,796 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 0.0059 ( 10 hom., cov: 32)
Exomes 𝑓: 0.00050 ( 7 hom. )

Consequence

CAPN2
NM_001748.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0230
Variant links:
Genes affected
CAPN2 (HGNC:1479): (calpain 2) 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 2. Multiple heterogeneous transcriptional start sites in the 5' UTR have been reported. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-223712784-C-T is Benign according to our data. Variant chr1-223712784-C-T is described in ClinVar as [Benign]. Clinvar id is 715900.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.023 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00588 (893/151988) while in subpopulation AFR AF= 0.0205 (853/41518). AF 95% confidence interval is 0.0194. There are 10 homozygotes in gnomad4. There are 403 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 10 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CAPN2NM_001748.5 linkuse as main transcriptc.144C>T p.Asp48= synonymous_variant 1/21 ENST00000295006.6
CAPN2XM_047431344.1 linkuse as main transcriptc.144C>T p.Asp48= synonymous_variant 1/12
CAPN2NM_001146068.2 linkuse as main transcriptc.4-4978C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CAPN2ENST00000295006.6 linkuse as main transcriptc.144C>T p.Asp48= synonymous_variant 1/211 NM_001748.5 P1P17655-1
CAPN2ENST00000433674.6 linkuse as main transcriptc.4-4978C>T intron_variant 2 P17655-2
CAPN2ENST00000434648.5 linkuse as main transcriptc.4-4978C>T intron_variant 5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00588
AC:
893
AN:
151880
Hom.:
10
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0206
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00223
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00240
GnomAD3 exomes
AF:
0.00112
AC:
230
AN:
205376
Hom.:
2
AF XY:
0.000730
AC XY:
82
AN XY:
112398
show subpopulations
Gnomad AFR exome
AF:
0.0197
Gnomad AMR exome
AF:
0.000376
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000214
Gnomad OTH exome
AF:
0.000210
GnomAD4 exome
AF:
0.000499
AC:
712
AN:
1426808
Hom.:
7
Cov.:
34
AF XY:
0.000380
AC XY:
269
AN XY:
708636
show subpopulations
Gnomad4 AFR exome
AF:
0.0203
Gnomad4 AMR exome
AF:
0.000418
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000124
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000820
Gnomad4 OTH exome
AF:
0.000965
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00588
AC:
893
AN:
151988
Hom.:
10
Cov.:
32
AF XY:
0.00542
AC XY:
403
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.0205
Gnomad4 AMR
AF:
0.00223
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00305
Hom.:
3
Bravo
AF:
0.00673
Asia WGS
AF:
0.00174
AC:
6
AN:
3460

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeApr 04, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
Cadd
Benign
12
Dann
Benign
0.87
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs28370008; hg19: chr1-223900486; API