chr10-113730350-G-A

Variant names:

• chr10-113730350-G-A
• rs1127687
• NM_001227.5:c.*810G>A

Variant summary

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

The NM_001227.5(CASP7):​c.*810G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,444 control chromosomes in the GnomAD database, including 4,288 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 0.23 (4281 hom., cov: 32)
  • Exomes 𝑓: 0.18 (7 hom.)
• Consequence: CASP7 NM_001227.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• Publications: 27 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 (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001227.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP7	NM_001227.5	MANE Select	c.*810G>A		3_prime_UTR	Exon 7 of 7	NP_001218.1
	CASP7	NM_001267057.1		c.*810G>A		3_prime_UTR	Exon 7 of 7	NP_001253986.1
	CASP7	NM_033338.6		c.*810G>A		3_prime_UTR	Exon 8 of 8	NP_203124.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP7	ENST00000369318.8	TSL:1 MANE Select	c.*810G>A		3_prime_UTR	Exon 7 of 7	ENSP00000358324.4
	CASP7	ENST00000621607.4	TSL:1	c.*810G>A		3_prime_UTR	Exon 7 of 7	ENSP00000478999.1
	CASP7	ENST00000345633.8	TSL:1	c.*810G>A		3_prime_UTR	Exon 8 of 8	ENSP00000298701.7

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35070 AN: 151994 Hom.: 4265 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.247

GnomAD4 exome AF: 0.184 AC: 61 AN: 332 Hom.: 7 Cov.: 0 AF XY: 0.185 AC XY: 43 AN XY: 232

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.156 AC: 20 AN: 128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.189 AC: 34 AN: 180

Other (OTH) AF: 0.300 AC: 3 AN: 10

GnomAD4 genome AF: 0.231 AC: 35122 AN: 152112 Hom.: 4281 Cov.: 32 AF XY: 0.226 AC XY: 16817 AN XY: 74366

African (AFR) AF: 0.295 AC: 12250 AN: 41492

American (AMR) AF: 0.173 AC: 2649 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 911 AN: 3470

East Asian (EAS) AF: 0.221 AC: 1140 AN: 5164

South Asian (SAS) AF: 0.221 AC: 1068 AN: 4822

European-Finnish (FIN) AF: 0.135 AC: 1427 AN: 10588

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14954 AN: 67962

Other (OTH) AF: 0.244 AC: 516 AN: 2114

Alfa AF: 0.225 Hom.: 11162

Bravo AF: 0.235

Asia WGS AF: 0.236 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.3
DANN	Benign	0.39
PhyloP100		-0.039
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: rs1127687; hg19: chr10-115490109;