16-547030-C-T

Variant names:

• chr16-547030-C-T
• rs775059866
• NM_005632.3:c.192C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS1

The NM_005632.3(CAPN15):​c.192C>T​(p.Cys64Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,456,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: CAPN15 NM_005632.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.298
• Publications: 0 publications found

Genes affected

CAPN15 (HGNC:11182): (calpain 15) This gene encodes a protein containing zinc-finger-like repeats and a calpain-like protease domain. The encoded protein may function as a transcription factor, RNA-binding protein, or in protein-protein interactions during visual system development. [provided by RefSeq, Jul 2008]

CAPN15 Gene-Disease associations (from GenCC):

• oculogastrointestinal-neurodevelopmental syndrome

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

ENSG00000261691 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 16-547030-C-T is Benign according to our data. Variant chr16-547030-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3034481.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.298 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.0000261 (38/1456874) while in subpopulation EAS AF = 0.000454 (18/39672). AF 95% confidence interval is 0.000293. There are 0 homozygotes in GnomAdExome4. There are 22 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPN15	NM_005632.3	c.192C>T	p.Cys64Cys	synonymous_variant	Exon 4 of 14	ENST00000219611.7	NP_005623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN15	ENST00000219611.7	c.192C>T	p.Cys64Cys	synonymous_variant	Exon 4 of 14	1	NM_005632.3	ENSP00000219611.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000165 AC: 4 AN: 242176 AF XY: 0.0000302

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000110

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000914

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000261 AC: 38 AN: 1456874 Hom.: 0 Cov.: 32 AF XY: 0.0000303 AC XY: 22 AN XY: 724906

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.000454 AC: 18 AN: 39672

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49434

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111470

Other (OTH) AF: 0.0000332 AC: 2 AN: 60272

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CAPN15-related disorder Benign:1

Jun 13, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.9
DANN	Benign	0.84
PhyloP100		-0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs775059866; hg19: chr16-597030; COSMIC: COSV99562549; COSMIC: COSV99562549;