rs62339863

Variant names:

• chr4-184649313-A-C
• rs62339863
• NM_004346.4:c.-183+82T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004346.4(CASP3):​c.-183+82T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 153,076 control chromosomes in the GnomAD database, including 7,079 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 0.29 (7025 hom., cov: 35)
  • Exomes 𝑓: 0.29 (54 hom.)
• Consequence: CASP3 NM_004346.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.96

Genes affected

CASP3 (HGNC:1504): (caspase 3) The protein encoded by this gene is a cysteine-aspartic acid protease that plays a central role in the execution-phase of cell apoptosis. The encoded protein cleaves and inactivates poly(ADP-ribose) polymerase while it cleaves and activates sterol regulatory element binding proteins as well as caspases 6, 7, and 9. This protein itself is processed by caspases 8, 9, and 10. It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimer's disease. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP3	NM_004346.4	c.-183+82T>G		intron_variant	Intron 1 of 7	ENST00000308394.9	NP_004337.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP3	ENST00000308394.9	c.-183+82T>G		intron_variant	Intron 1 of 7	1	NM_004346.4	ENSP00000311032.4

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43404 AN: 151892 Hom.: 7020 Cov.: 35

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.333

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.313

GnomAD4 exome AF: 0.286 AC: 305 AN: 1066 Hom.: 54 AF XY: 0.268 AC XY: 175 AN XY: 654

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.667

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.583

Gnomad4 SAS exome AF: 0.625

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.246

Gnomad4 OTH exome AF: 0.283

GnomAD4 genome AF: 0.286 AC: 43442 AN: 152010 Hom.: 7025 Cov.: 35 AF XY: 0.294 AC XY: 21847 AN XY: 74296

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.311

Alfa AF: 0.270 Hom.: 710

Bravo AF: 0.294

Asia WGS AF: 0.502 AC: 1742 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.024
DANN	Benign	0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs62339863; hg19: chr4-185570467; COSMIC: COSV57725942; COSMIC: COSV57725942;