10-113679771-G-C

Variant names:

• chr10-113679771-G-C
• rs28411397
• ENST00000345633.8:c.-282G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000345633.8(CASP7):​c.-282G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,304,694 control chromosomes in the GnomAD database, including 47,013 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 0.24 (4680 hom., cov: 33)
  • Exomes 𝑓: 0.27 (42333 hom.)
• Consequence: CASP7 ENST00000345633.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 15 publications found

Genes affected

CASP7 (HGNC:1508): (caspase 7) This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. The precursor of the encoded protein is cleaved by caspase 3 and 10, is activated upon cell death stimuli and induces apoptosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.4609098E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP7	NM_001227.5	c.-208G>C		upstream_gene_variant		ENST00000369318.8	NP_001218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8	c.-208G>C		upstream_gene_variant		1	NM_001227.5	ENSP00000358324.4

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36240 AN: 151990 Hom.: 4674 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.249

GnomAD2 exomes AF: 0.311 AC: 6102 AN: 19630 AF XY: 0.306

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.306

Gnomad ASJ exome AF: 0.244

Gnomad EAS exome AF: 0.488

Gnomad FIN exome AF: 0.335

Gnomad NFE exome AF: 0.290

Gnomad OTH exome AF: 0.285

GnomAD4 exome AF: 0.266 AC: 306632 AN: 1152588 Hom.: 42333 Cov.: 30 AF XY: 0.266 AC XY: 147447 AN XY: 553608

African (AFR) AF: 0.145 AC: 3456 AN: 23856

American (AMR) AF: 0.299 AC: 4091 AN: 13684

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 3104 AN: 15932

East Asian (EAS) AF: 0.463 AC: 12862 AN: 27768

South Asian (SAS) AF: 0.289 AC: 12331 AN: 42694

European-Finnish (FIN) AF: 0.290 AC: 7526 AN: 25954

Middle Eastern (MID) AF: 0.240 AC: 758 AN: 3154

European-Non Finnish (NFE) AF: 0.263 AC: 250361 AN: 952826

Other (OTH) AF: 0.260 AC: 12143 AN: 46720

GnomAD4 genome AF: 0.238 AC: 36260 AN: 152106 Hom.: 4680 Cov.: 33 AF XY: 0.242 AC XY: 17975 AN XY: 74326

African (AFR) AF: 0.150 AC: 6214 AN: 41546

American (AMR) AF: 0.262 AC: 4006 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 630 AN: 3468

East Asian (EAS) AF: 0.423 AC: 2171 AN: 5130

South Asian (SAS) AF: 0.297 AC: 1429 AN: 4818

European-Finnish (FIN) AF: 0.283 AC: 2990 AN: 10564

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17843 AN: 67964

Other (OTH) AF: 0.251 AC: 530 AN: 2110

Alfa AF: 0.168 Hom.: 596

Bravo AF: 0.234

TwinsUK AF: 0.245 AC: 907

ALSPAC AF: 0.264 AC: 1016

ExAC AF: 0.171 AC: 2139

Asia WGS AF: 0.322 AC: 1117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.37
DANN	Benign	0.40
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.00079	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.00015	T
PhyloP100		-2.2
PrimateAI	Uncertain	0.57	T
Vest4		0.10
GERP RS		-4.4
PromoterAI		-0.081	Neutral
gMVP		0.10
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: rs28411397; hg19: chr10-115439530; COSMIC: COSV61881043; COSMIC: COSV61881043;