rs12038826

Variant names:

• chr1-230787205-T-C
• rs12038826
• NM_006615.3:c.1519-317T>C

Variant summary

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

The NM_006615.3(CAPN9):​c.1519-317T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0697 in 152,222 control chromosomes in the GnomAD database, including 399 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 0.070 (399 hom., cov: 32)
• Consequence: CAPN9 NM_006615.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264
• Publications: 7 publications found

Genes affected

CAPN9 (HGNC:1486): (calpain 9) Calpains are ubiquitous, well-conserved family of calcium-dependent, cysteine proteases. The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large subunit possesses a cysteine protease domain, and both subunits possess calcium-binding domains. Calpains have been implicated in neurodegenerative processes, as their activation can be triggered by calcium influx and oxidative stress. The protein encoded by this gene is expressed predominantly in stomach and small intestine and may have specialized functions in the digestive tract. This gene is thought to be associated with gastric cancer. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000244137 (HGNC:58238):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPN9	NM_006615.3	c.1519-317T>C		intron_variant	Intron 12 of 19	ENST00000271971.7	NP_006606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN9	ENST00000271971.7	c.1519-317T>C		intron_variant	Intron 12 of 19	1	NM_006615.3	ENSP00000271971.2

Frequencies

GnomAD3 genomes AF: 0.0697 AC: 10600 AN: 152104 Hom.: 399 Cov.: 32

Gnomad AFR AF: 0.0873

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0387

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.0754

Gnomad SAS AF: 0.0648

Gnomad FIN AF: 0.0674

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0698

Gnomad OTH AF: 0.0474

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

GnomAD4 genome AF: 0.0697 AC: 10605 AN: 152222 Hom.: 399 Cov.: 32 AF XY: 0.0694 AC XY: 5166 AN XY: 74428

African (AFR) AF: 0.0873 AC: 3623 AN: 41518

American (AMR) AF: 0.0386 AC: 590 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0233 AC: 81 AN: 3472

East Asian (EAS) AF: 0.0756 AC: 391 AN: 5174

South Asian (SAS) AF: 0.0651 AC: 314 AN: 4824

European-Finnish (FIN) AF: 0.0674 AC: 715 AN: 10608

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0698 AC: 4748 AN: 68012

Other (OTH) AF: 0.0469 AC: 99 AN: 2112

Alfa AF: 0.0694 Hom.: 1343

Bravo AF: 0.0690

Asia WGS AF: 0.0710 AC: 248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.58
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12038826; hg19: chr1-230922951;