rs35372903

Variant names:

• chr4-184649279-G-A
• rs35372903
• NM_004346.4:c.-183+116C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-184649279-G-A
• chr4-184649279-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_004346.4(CASP3):​c.-183+116C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0452 in 152,586 control chromosomes in the GnomAD database, including 465 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 0.045 (465 hom., cov: 34)
  • Exomes 𝑓: 0.0088 (0 hom.)
• Consequence: CASP3 NM_004346.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.908

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP3	NM_004346.4	c.-183+116C>T		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+116C>T		intron_variant	Intron 1 of 7	1	NM_004346.4	ENSP00000311032.4

Frequencies

GnomAD3 genomes AF: 0.0453 AC: 6883 AN: 152014 Hom.: 465 Cov.: 34

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0213

Gnomad ASJ AF: 0.0325

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.000566

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.00210

Gnomad OTH AF: 0.0345

GnomAD4 exome AF: 0.00877 AC: 4 AN: 456 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 276

Gnomad4 AFR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00294

Gnomad4 OTH exome AF: 0.0385

GnomAD4 genome AF: 0.0453 AC: 6888 AN: 152130 Hom.: 465 Cov.: 34 AF XY: 0.0435 AC XY: 3237 AN XY: 74358

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0212

Gnomad4 ASJ AF: 0.0325

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000566

Gnomad4 NFE AF: 0.00210

Gnomad4 OTH AF: 0.0341

Alfa AF: 0.0229 Hom.: 31

Bravo AF: 0.0521

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.4
DANN	Benign	0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.28		Position offset: 2

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

Publications

LitVar

Other links and lift over

dbSNP: rs35372903; hg19: chr4-185570433;