chrX-111251300-G-GAA

Variant names:

• chrX-111251300-G-GAA
• rs201147886
• NM_014289.4:c.894-16_894-15dupTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_014289.4(CAPN6):​c.894-16_894-15dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., 19 hem., cov: 18)
  • Exomes 𝑓: 0.0014 (0 hom. 2 hem.)
• Consequence: CAPN6 NM_014289.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31

Genes affected

CAPN6 (HGNC:1483): (calpain 6) 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 highly expressed in the placenta. Its C-terminal region lacks any homology to the calmodulin-like domain of other calpains. The protein lacks critical active site residues and thus is suggested to be proteolytically inactive. The protein may play a role in tumor formation by inhibiting apoptosis and promoting angiogenesis. [provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0014 (1161/831332) while in subpopulation AFR AF= 0.0315 (593/18833). AF 95% confidence interval is 0.0294. There are 0 homozygotes in gnomad4_exome. There are 2 alleles in male gnomad4_exome subpopulation. Median coverage is 10. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPN6	NM_014289.4	c.894-16_894-15dupTT		intron_variant	Intron 6 of 12	ENST00000324068.2	NP_055104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN6	ENST00000324068.2	c.894-15_894-14insTT		intron_variant	Intron 6 of 12	1	NM_014289.4	ENSP00000317214.1

Frequencies

GnomAD3 genomes AF: 0.00117 AC: 100 AN: 85806 Hom.: 0 Cov.: 18 AF XY: 0.000929 AC XY: 19 AN XY: 20444

Gnomad AFR AF: 0.00376

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000522

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000481

Gnomad OTH AF: 0.000890

GnomAD3 exomes AF: 0.00540 AC: 244 AN: 45184 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2042

Gnomad AFR exome AF: 0.0321

Gnomad AMR exome AF: 0.00272

Gnomad ASJ exome AF: 0.00310

Gnomad EAS exome AF: 0.000618

Gnomad SAS exome AF: 0.000657

Gnomad FIN exome AF: 0.00232

Gnomad NFE exome AF: 0.00186

Gnomad OTH exome AF: 0.00178

GnomAD4 exome AF: 0.00140 AC: 1161 AN: 831332 Hom.: 0 Cov.: 10 AF XY: 0.00000803 AC XY: 2 AN XY: 249046

Gnomad4 AFR exome AF: 0.0315

Gnomad4 AMR exome AF: 0.00113

Gnomad4 ASJ exome AF: 0.000786

Gnomad4 EAS exome AF: 0.0000780

Gnomad4 SAS exome AF: 0.000466

Gnomad4 FIN exome AF: 0.000270

Gnomad4 NFE exome AF: 0.000661

Gnomad4 OTH exome AF: 0.00217

GnomAD4 genome AF: 0.00117 AC: 100 AN: 85804 Hom.: 0 Cov.: 18 AF XY: 0.000929 AC XY: 19 AN XY: 20456

Gnomad4 AFR AF: 0.00376

Gnomad4 AMR AF: 0.000521

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000481

Gnomad4 OTH AF: 0.000880

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201147886; hg19: chrX-110494528;