rs2266928

Positions:

• chr16-530124-C-A
• chr16-530124-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAPN15	NM_005632.3	c.-190+2095C>A		intron_variant		ENST00000219611.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAPN15	ENST00000219611.7	c.-190+2095C>A		intron_variant		1	NM_005632.3	P1
CAPN15	ENST00000567216.5	n.282+2095C>A		intron_variant, non_coding_transcript_variant		1
CAPN15	ENST00000562370.5	c.-76+2095C>A		intron_variant		2
CAPN15	ENST00000568988.5	c.-368+2095C>A		intron_variant		3

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

Gnomad4 AFR AF: 0.556

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.229

Alfa AF: 0.144 Hom.: 2792

Bravo AF: 0.274

Asia WGS AF: 0.267 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.74
DANN	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2266928; hg19: chr16-580124;