rs2720379

chr4-184648118-G-Achr4-184648118-G-Cchr4-184648118-G-T

Variant summary

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

The NM_004346.4(CASP3):c.-16+347C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,992 control chromosomes in the GnomAD database, including 20,688 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 0.47 (20688 hom., cov: 31)
• Consequence: CASP3 NM_004346.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.971

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP3	NM_004346.4	c.-16+347C>T		intron_variant		ENST00000308394.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP3	ENST00000308394.9	c.-16+347C>T		intron_variant		1	NM_004346.4	P1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71557 AN: 151872 Hom.: 20635 Cov.: 31

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.451

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.472 AC: 71681 AN: 151992 Hom.: 20688 Cov.: 31 AF XY: 0.474 AC XY: 35210 AN XY: 74308

Gnomad4 AFR AF: 0.799

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.452

Alfa AF: 0.366 Hom.: 2032

Bravo AF: 0.504

Asia WGS AF: 0.532 AC: 1851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.0
Dann	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs2720379; hg19: chr4-185569272;