16-530124-C-A

Variant names:

• chr16-530124-C-A
• rs2266928
• NM_005632.3:c.-190+2095C>A

Variant summary

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

The NM_005632.3(CAPN15):​c.-190+2095C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,054 control chromosomes in the GnomAD database, including 7,846 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 0.26 (7846 hom., cov: 33)
• Consequence: CAPN15 NM_005632.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.924
• Publications: 18 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005632.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN15	NM_005632.3	MANE Select	c.-190+2095C>A		intron	N/A	NP_005623.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN15	ENST00000219611.7	TSL:1 MANE Select	c.-190+2095C>A		intron	N/A	ENSP00000219611.2
	CAPN15	ENST00000567216.5	TSL:1	n.282+2095C>A		intron	N/A
	CAPN15	ENST00000871914.1		c.-76+692C>A		intron	N/A	ENSP00000541973.1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39193 AN: 151936 Hom.: 7833 Cov.: 33

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.258 AC: 39245 AN: 152054 Hom.: 7846 Cov.: 33 AF XY: 0.254 AC XY: 18884 AN XY: 74342

African (AFR) AF: 0.556 AC: 23013 AN: 41404

American (AMR) AF: 0.139 AC: 2123 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 530 AN: 3472

East Asian (EAS) AF: 0.386 AC: 1997 AN: 5172

South Asian (SAS) AF: 0.103 AC: 496 AN: 4828

European-Finnish (FIN) AF: 0.134 AC: 1421 AN: 10590

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8913 AN: 67986

Other (OTH) AF: 0.229 AC: 483 AN: 2108

Alfa AF: 0.157 Hom.: 8637

Bravo AF: 0.274

Asia WGS AF: 0.267 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.74
DANN	Benign	0.43
PhyloP100		-0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2266928; hg19: chr16-580124;