4-184636744-TAAATCCTGAA-TAAATCCTGAAAAATCCTGAA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_004346.4(CASP3):​c.54-1336_54-1327dupTTCAGGATTT 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 NM_004346.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• Publications: 5 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

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_54-1327dupTTCAGGATTT		intron	N/A	NP_004337.2
	CASP3	NM_001354777.2		c.54-1336_54-1327dupTTCAGGATTT		intron	N/A	NP_001341706.1
	CASP3	NM_032991.3		c.54-1336_54-1327dupTTCAGGATTT		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.54-1327_54-1326insTTCAGGATTT		intron	N/A	ENSP00000311032.4
	CASP3	ENST00000523916.5	TSL:1	c.54-1327_54-1326insTTCAGGATTT		intron	N/A	ENSP00000428929.1
	CASP3	ENST00000393585.6	TSL:1	c.54-1327_54-1326insTTCAGGATTT		intron	N/A	ENSP00000377210.2

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

African (AFR) AF: 0.108 AC: 4477 AN: 41514

American (AMR) AF: 0.274 AC: 4171 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0915 AC: 317 AN: 3466

East Asian (EAS) AF: 0.700 AC: 3569 AN: 5096

South Asian (SAS) AF: 0.285 AC: 1371 AN: 4804

European-Finnish (FIN) AF: 0.175 AC: 1855 AN: 10596

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.114 AC: 7743 AN: 67996

Other (OTH) AF: 0.141 AC: 298 AN: 2114

Alfa AF: 0.131 Hom.: 124

Asia WGS AF: 0.443 AC: 1539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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;