rs1933633

Variant names:

• chr1-230788630-G-A
• rs1933633
• NM_006615.3:c.1599+1028G>A

Variant summary

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

The NM_006615.3(CAPN9):​c.1599+1028G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,168 control chromosomes in the GnomAD database, including 2,265 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 0.17 (2265 hom., cov: 32)
• Consequence: CAPN9 NM_006615.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• Publications: 2 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 (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPN9	NM_006615.3	c.1599+1028G>A		intron_variant	Intron 13 of 19	ENST00000271971.7	NP_006606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN9	ENST00000271971.7	c.1599+1028G>A		intron_variant	Intron 13 of 19	1	NM_006615.3	ENSP00000271971.2

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25504 AN: 152050 Hom.: 2265 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0831

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.168 AC: 25521 AN: 152168 Hom.: 2265 Cov.: 32 AF XY: 0.167 AC XY: 12408 AN XY: 74382

African (AFR) AF: 0.137 AC: 5686 AN: 41518

American (AMR) AF: 0.151 AC: 2310 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 768 AN: 3468

East Asian (EAS) AF: 0.0829 AC: 430 AN: 5184

South Asian (SAS) AF: 0.200 AC: 964 AN: 4814

European-Finnish (FIN) AF: 0.196 AC: 2075 AN: 10602

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12698 AN: 67984

Other (OTH) AF: 0.183 AC: 386 AN: 2114

Alfa AF: 0.186 Hom.: 4570

Bravo AF: 0.163

Asia WGS AF: 0.140 AC: 488 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	1.6
DANN	Benign	0.74
PhyloP100		-0.088
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: rs1933633; hg19: chr1-230924376;