rs1042891

Variant names:

• chr4-109688930-A-G
• rs1042891
• NM_001226.4:c.*400T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-109688930-A-G
• chr4-109688930-A-T

Variant summary

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

The NM_001226.4(CASP6):​c.*400T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 156,256 control chromosomes in the GnomAD database, including 37,276 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 0.69 (36217 hom., cov: 28)
  • Exomes 𝑓: 0.62 (1059 hom.)
• Consequence: CASP6 NM_001226.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• Publications: 10 publications found

Genes affected

CASP6 (HGNC:1507): (caspase 6) This gene encodes a member of the cysteine-aspartic acid protease (caspase) family of enzymes. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic acid residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein is processed by caspases 7, 8 and 10, and is thought to function as a downstream enzyme in the caspase activation cascade. Alternative splicing of this gene results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Oct 2015]

MCUB (HGNC:26076): (mitochondrial calcium uniporter dominant negative subunit beta) Predicted to enable calcium channel inhibitor activity. Predicted to be involved in calcium import into the mitochondrion and mitochondrial calcium ion homeostasis. Located in mitochondrion and nucleoplasm. Is integral component of mitochondrial inner membrane. Part of uniplex complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001226.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP6	NM_001226.4	MANE Select	c.*400T>C		3_prime_UTR	Exon 7 of 7	NP_001217.2
	CASP6	NR_133012.2		n.1255T>C		non_coding_transcript_exon	Exon 6 of 6
	CASP6	NM_032992.3		c.*400T>C		3_prime_UTR	Exon 4 of 4	NP_116787.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP6	ENST00000265164.7	TSL:1 MANE Select	c.*400T>C		3_prime_UTR	Exon 7 of 7	ENSP00000265164.2
	CASP6	ENST00000352981.7	TSL:1	c.*400T>C		3_prime_UTR	Exon 4 of 4	ENSP00000285333.3
	CASP6	ENST00000505486.2		n.*962T>C		non_coding_transcript_exon	Exon 6 of 6	ENSP00000424080.1

Frequencies

GnomAD3 genomes AF: 0.689 AC: 103901 AN: 150788 Hom.: 36169 Cov.: 28

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.669

GnomAD4 exome AF: 0.615 AC: 3298 AN: 5362 Hom.: 1059 Cov.: 0 AF XY: 0.611 AC XY: 1699 AN XY: 2780

African (AFR) AF: 0.662 AC: 45 AN: 68

American (AMR) AF: 0.586 AC: 684 AN: 1168

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 38 AN: 88

East Asian (EAS) AF: 0.463 AC: 173 AN: 374

South Asian (SAS) AF: 0.668 AC: 393 AN: 588

European-Finnish (FIN) AF: 0.565 AC: 26 AN: 46

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.642 AC: 1822 AN: 2840

Other (OTH) AF: 0.616 AC: 117 AN: 190

GnomAD4 genome AF: 0.689 AC: 104000 AN: 150894 Hom.: 36217 Cov.: 28 AF XY: 0.686 AC XY: 50519 AN XY: 73602

African (AFR) AF: 0.783 AC: 32142 AN: 41040

American (AMR) AF: 0.620 AC: 9428 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2070 AN: 3466

East Asian (EAS) AF: 0.534 AC: 2727 AN: 5108

South Asian (SAS) AF: 0.739 AC: 3547 AN: 4802

European-Finnish (FIN) AF: 0.673 AC: 6824 AN: 10136

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45040 AN: 67830

Other (OTH) AF: 0.673 AC: 1415 AN: 2104

Alfa AF: 0.681 Hom.: 12665

Bravo AF: 0.687

Asia WGS AF: 0.702 AC: 2439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.36
DANN	Benign	0.45
PhyloP100		-1.7
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: rs1042891; hg19: chr4-110610086; COSMIC: COSV54461286; COSMIC: COSV54461286;