X-111251300-G-GA

Variant names:

• chrX-111251300-G-GA
• rs201147886
• NM_014289.4:c.894-15dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014289.4(CAPN6):​c.894-15dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (2090 hom., 2243 hem., cov: 18)
  • Exomes 𝑓: 0.16 (124 hom. 374 hem.)
• Consequence: CAPN6 NM_014289.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.31
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant X-111251300-G-GA is Benign according to our data. Variant chrX-111251300-G-GA is described in ClinVar as Benign. ClinVar VariationId is 1250758.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014289.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN6	NM_014289.4	MANE Select	c.894-15dupT		intron	N/A	NP_055104.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN6	ENST00000324068.2	TSL:1 MANE Select	c.894-15_894-14insT		intron	N/A	ENSP00000317214.1	Q9Y6Q1
	CAPN6	ENST00000932651.1		c.492-15_492-14insT		intron	N/A	ENSP00000602710.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 12284 AN: 85624 Hom.: 2087 Cov.: 18

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.00854

Gnomad EAS AF: 0.00109

Gnomad SAS AF: 0.00690

Gnomad FIN AF: 0.00773

Gnomad MID AF: 0.0741

Gnomad NFE AF: 0.00906

Gnomad OTH AF: 0.112

GnomAD2 exomes AF: 0.234 AC: 10592 AN: 45184 AF XY: 0.0260

Gnomad AFR exome AF: 0.430

Gnomad AMR exome AF: 0.264

Gnomad ASJ exome AF: 0.232

Gnomad EAS exome AF: 0.220

Gnomad FIN exome AF: 0.190

Gnomad NFE exome AF: 0.186

Gnomad OTH exome AF: 0.233

GnomAD4 exome AF: 0.156 AC: 97323 AN: 622828 Hom.: 124 Cov.: 10 AF XY: 0.00253 AC XY: 374 AN XY: 147590

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.390 AC: 6327 AN: 16213

American (AMR) AF: 0.155 AC: 2557 AN: 16444

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 1560 AN: 10728

East Asian (EAS) AF: 0.122 AC: 2032 AN: 16695

South Asian (SAS) AF: 0.105 AC: 2732 AN: 25965

European-Finnish (FIN) AF: 0.110 AC: 2533 AN: 23132

Middle Eastern (MID) AF: 0.122 AC: 269 AN: 2200

European-Non Finnish (NFE) AF: 0.154 AC: 74812 AN: 484930

Other (OTH) AF: 0.170 AC: 4501 AN: 26521

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.144 AC: 12295 AN: 85620 Hom.: 2090 Cov.: 18 AF XY: 0.110 AC XY: 2243 AN XY: 20396

African (AFR) AF: 0.452 AC: 11153 AN: 24702

American (AMR) AF: 0.0748 AC: 573 AN: 7658

Ashkenazi Jewish (ASJ) AF: 0.00854 AC: 18 AN: 2108

East Asian (EAS) AF: 0.00109 AC: 3 AN: 2741

South Asian (SAS) AF: 0.00588 AC: 11 AN: 1870

European-Finnish (FIN) AF: 0.00773 AC: 25 AN: 3234

Middle Eastern (MID) AF: 0.0698 AC: 12 AN: 172

European-Non Finnish (NFE) AF: 0.00906 AC: 376 AN: 41483

Other (OTH) AF: 0.110 AC: 124 AN: 1125

Alfa AF: 0.0447 Hom.: 4

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.3
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: rs201147886; hg19: chrX-110494528;