rs4647655

Variant names:

• chr4-184636744-TAAATCCTGAA-T
• rs4647655
• NM_004346.4:c.54-1336_54-1327delTTCAGGATTT

Your query was ambiguous. Multiple possible variants found:

• chr4-184636744-TAAATCCTGAA-T
• chr4-184636744-TAAATCCTGAA-TAAATCCTGAAAAATCCTGAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004346.4(CASP3):​c.54-1336_54-1327delTTCAGGATTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 29)
• Consequence: CASP3 NM_004346.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.971
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004346.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP3	NM_004346.4	MANE Select	c.54-1336_54-1327delTTCAGGATTT		intron	N/A	NP_004337.2
	CASP3	NM_001354777.2		c.54-1336_54-1327delTTCAGGATTT		intron	N/A	NP_001341706.1
	CASP3	NM_032991.3		c.54-1336_54-1327delTTCAGGATTT		intron	N/A	NP_116786.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP3	ENST00000308394.9	TSL:1 MANE Select	c.54-1336_54-1327delTTCAGGATTT		intron	N/A	ENSP00000311032.4
	CASP3	ENST00000523916.5	TSL:1	c.54-1336_54-1327delTTCAGGATTT		intron	N/A	ENSP00000428929.1
	CASP3	ENST00000393585.6	TSL:1	c.54-1336_54-1327delTTCAGGATTT		intron	N/A	ENSP00000377210.2

Frequencies

GnomAD3 genomes Cov.: 29

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

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.97

Splicing

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

Other links and lift over

dbSNP: rs4647655; hg19: chr4-185557898;