4-184636744-TAAATCCTGAA-TAAATCCTGAAAAATCCTGAA

Position:

• chr4-184636744-TAAATCCTGAA-TAAATCCTGAAAAATCCTGAA

Variant summary

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

The ENST00000308394.9(CASP3):​c.54-1327_54-1326insTTCAGGATTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,036 control chromosomes in the GnomAD database, including 2,971 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2971 hom., cov: 29)
• Consequence: CASP3 ENST00000308394.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211

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 (EAS) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP3	NM_004346.4	c.54-1327_54-1326insTTCAGGATTT		intron_variant		ENST00000308394.9	NP_004337.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP3	ENST00000308394.9	c.54-1327_54-1326insTTCAGGATTT		intron_variant		1	NM_004346.4	ENSP00000311032	P1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23929 AN: 151920 Hom.: 2965 Cov.: 29

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.0915

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.158 AC: 23950 AN: 152036 Hom.: 2971 Cov.: 29 AF XY: 0.168 AC XY: 12498 AN XY: 74338

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.0915

Gnomad4 EAS AF: 0.700

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.141

Alfa AF: 0.131 Hom.: 124

Asia WGS AF: 0.443 AC: 1539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4647655; hg19: chr4-185557898;