rs2720379

Variant names:

• chr4-184648118-G-A
• rs2720379
• NM_004346.4:c.-16+347C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-184648118-G-A
• chr4-184648118-G-C
• chr4-184648118-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 -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.

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.-16+347C>T		intron	N/A	NP_004337.2
	CASP3	NM_001354777.2		c.-16+385C>T		intron	N/A	NP_001341706.1	P42574
	CASP3	NM_032991.3		c.-16+1277C>T		intron	N/A	NP_116786.1	P42574

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP3	ENST00000308394.9	TSL:1 MANE Select	c.-16+347C>T		intron	N/A	ENSP00000311032.4	P42574
	CASP3	ENST00000523916.5	TSL:1	c.-16+1277C>T		intron	N/A	ENSP00000428929.1	P42574
	CASP3	ENST00000393585.6	TSL:1	c.-208+347C>T		intron	N/A	ENSP00000377210.2	A8MVM1

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

African (AFR) AF: 0.799 AC: 33131 AN: 41472

American (AMR) AF: 0.497 AC: 7582 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1234 AN: 3470

East Asian (EAS) AF: 0.679 AC: 3497 AN: 5154

South Asian (SAS) AF: 0.397 AC: 1913 AN: 4818

European-Finnish (FIN) AF: 0.298 AC: 3146 AN: 10568

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19844 AN: 67940

Other (OTH) AF: 0.452 AC: 951 AN: 2106

Alfa AF: 0.394 Hom.: 4676

Bravo AF: 0.504

Asia WGS AF: 0.532 AC: 1851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.0
DANN	Benign	0.72
PhyloP100		-0.97
PromoterAI		-0.021	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2720379; hg19: chr4-185569272;