chr10-113679771-G-C

Variant names:

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

Variant summary

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

The NM_001267057.1(CASP7):​c.17G>C​(p.Arg6Pro) variant causes a missense 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. 8/11 in silico tools predict 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 NM_001267057.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21

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

Verdict is Benign. Variant got -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_001267057.1	c.17G>C	p.Arg6Pro	missense_variant	Exon 1 of 7		NP_001253986.1
CASP7	NM_001320911.2	c.-8+422G>C		intron_variant	Intron 1 of 6		NP_001307840.1
CASP7	NM_001267056.2	c.-1+422G>C		intron_variant	Intron 1 of 6		NP_001253985.1
CASP7	NM_033340.4	c.-1+422G>C		intron_variant	Intron 1 of 7		NP_203126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000345633	c.-282G>C		5_prime_UTR_variant	Exon 1 of 8	1		ENSP00000298701.7
CASP7	ENST00000621345.4	c.-1+422G>C		intron_variant	Intron 1 of 6	1		ENSP00000480584.1
CASP7	ENST00000369331.8	c.-1+422G>C		intron_variant	Intron 1 of 7	1		ENSP00000358337.3

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

GnomAD3 exomes AF: 0.311 AC: 6102 AN: 19630 Hom.: 1017 AF XY: 0.306 AC XY: 3302 AN XY: 10800

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 SAS exome AF: 0.329

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

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.299

Gnomad4 ASJ exome AF: 0.195

Gnomad4 EAS exome AF: 0.463

Gnomad4 SAS exome AF: 0.289

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.263

Gnomad4 OTH exome AF: 0.260

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

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.251

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
PrimateAI	Uncertain	0.57	T
Vest4		0.10
GERP RS		-4.4
gMVP		0.10

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: rs28411397; hg19: chr10-115439530; COSMIC: COSV61881043; COSMIC: COSV61881043;