rs3814231

Variant names:

• chr10-113721259-C-A
• rs3814231
• NM_001227.5:c.247+91C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-113721259-C-A
• chr10-113721259-C-G
• chr10-113721259-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001227.5(CASP7):​c.247+91C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000848 in 1,178,720 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: CASP7 NM_001227.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.748
• Publications: 0 publications found

Genes affected

CASP7 (HGNC:1508): (caspase 7) This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. 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 residues to produce two subunits, large and small, that dimerize to form the active enzyme. The precursor of the encoded protein is cleaved by caspase 3 and 10, is activated upon cell death stimuli and induces apoptosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP7	NM_001227.5	c.247+91C>A		intron_variant	Intron 3 of 6	ENST00000369318.8	NP_001218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8	c.247+91C>A		intron_variant	Intron 3 of 6	1	NM_001227.5	ENSP00000358324.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.48e-7 AC: 1 AN: 1178720 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 587334

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

African (AFR) AF: 0.00 AC: 0 AN: 26454

American (AMR) AF: 0.00 AC: 0 AN: 31076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19302

East Asian (EAS) AF: 0.00 AC: 0 AN: 38078

South Asian (SAS) AF: 0.0000152 AC: 1 AN: 65648

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4948

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 893238

Other (OTH) AF: 0.00 AC: 0 AN: 50080

⚠️ 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 Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.75
DANN	Benign	0.51
PhyloP100		-0.75

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: rs3814231; hg19: chr10-115481018;