NM_032982.4:c.74+1276T>G

Variant names:

• chr7-143289805-T-G
• rs3181166
• NM_032982.4:c.74+1276T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032982.4(CASP2):​c.74+1276T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 167,334 control chromosomes in the GnomAD database, including 1,529 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 0.12 (1366 hom., cov: 32)
  • Exomes 𝑓: 0.12 (163 hom.)
• Consequence: CASP2 NM_032982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121

Genes affected

CASP2 (HGNC:1503): (caspase 2) This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Caspases mediate cellular apoptosis through the proteolytic cleavage of specific protein substrates. The encoded protein may function in stress-induced cell death pathways, cell cycle maintenance, and the suppression of tumorigenesis. Increased expression of this gene may play a role in neurodegenerative disorders including Alzheimer's disease, Huntington's disease and temporal lobe epilepsy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP2	NM_032982.4	c.74+1276T>G		intron_variant	Intron 1 of 10	ENST00000310447.10	NP_116764.2
CASP2	NM_001224.5	c.-20+149T>G		intron_variant	Intron 1 of 11		NP_001215.1
CASP2	NM_032983.4	c.74+1276T>G		intron_variant	Intron 1 of 9		NP_116765.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP2	ENST00000310447.10	c.74+1276T>G		intron_variant	Intron 1 of 10	1	NM_032982.4	ENSP00000312664.5

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17529 AN: 152104 Hom.: 1368 Cov.: 32

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0831

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.0989

GnomAD4 exome AF: 0.120 AC: 1815 AN: 15112 Hom.: 163 AF XY: 0.121 AC XY: 890 AN XY: 7370

Gnomad4 AFR exome AF: 0.0246

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0588

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.102

GnomAD4 genome AF: 0.115 AC: 17526 AN: 152222 Hom.: 1366 Cov.: 32 AF XY: 0.116 AC XY: 8667 AN XY: 74430

Gnomad4 AFR AF: 0.0314

Gnomad4 AMR AF: 0.0829

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.0110

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.0978

Alfa AF: 0.153 Hom.: 878

Bravo AF: 0.101

Asia WGS AF: 0.0880 AC: 305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0
DANN	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs3181166; hg19: chr7-142986898;