chr10-113709362-GAGA-G

Variant names:

• chr10-113709362-GAGA-G
• rs767845230
• NM_001227.5:c.111-11664_111-11662delAAG

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001227.5(CASP7):​c.111-11664_111-11662delAAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,497,066 control chromosomes in the GnomAD database, including 51 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (9 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (42 hom.)
• Consequence: CASP7 NM_001227.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.43
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 10-113709362-GAGA-G is Benign according to our data. Variant chr10-113709362-GAGA-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2640853.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 282 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP7	NM_001227.5	MANE Select	c.111-11664_111-11662delAAG		intron	N/A	NP_001218.1	P55210-1
	CASP7	NM_001267057.1		c.335-11633_335-11631delAAG		intron	N/A	NP_001253986.1	P55210
	CASP7	NM_033338.6		c.210-11664_210-11662delAAG		intron	N/A	NP_203124.1	P55210-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP7	ENST00000369318.8	TSL:1 MANE Select	c.111-11664_111-11662delAAG		intron	N/A	ENSP00000358324.4	P55210-1
	CASP7	ENST00000621607.4	TSL:1	c.210-11664_210-11662delAAG		intron	N/A	ENSP00000478999.1	P55210-3
	CASP7	ENST00000345633.8	TSL:1	c.111-11664_111-11662delAAG		intron	N/A	ENSP00000298701.7	P55210-1

Frequencies

GnomAD3 genomes AF: 0.00185 AC: 281 AN: 152210 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000808

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00489 AC: 501 AN: 102398 AF XY: 0.00487

Gnomad AFR exome AF: 0.000193

Gnomad AMR exome AF: 0.00114

Gnomad ASJ exome AF: 0.0497

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000234

Gnomad NFE exome AF: 0.00136

Gnomad OTH exome AF: 0.00479

GnomAD4 exome AF: 0.00191 AC: 2570 AN: 1344738 Hom.: 42 AF XY: 0.00212 AC XY: 1406 AN XY: 662192

African (AFR) AF: 0.000167 AC: 5 AN: 29918

American (AMR) AF: 0.000724 AC: 22 AN: 30402

Ashkenazi Jewish (ASJ) AF: 0.0479 AC: 1105 AN: 23060

East Asian (EAS) AF: 0.0000574 AC: 2 AN: 34852

South Asian (SAS) AF: 0.00620 AC: 446 AN: 71884

European-Finnish (FIN) AF: 0.0000311 AC: 1 AN: 32194

Middle Eastern (MID) AF: 0.00562 AC: 31 AN: 5516

European-Non Finnish (NFE) AF: 0.000619 AC: 657 AN: 1060732

Other (OTH) AF: 0.00536 AC: 301 AN: 56180

GnomAD4 genome AF: 0.00185 AC: 282 AN: 152328 Hom.: 9 Cov.: 33 AF XY: 0.00184 AC XY: 137 AN XY: 74480

African (AFR) AF: 0.0000241 AC: 1 AN: 41574

American (AMR) AF: 0.000327 AC: 5 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0542 AC: 188 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000808 AC: 55 AN: 68032

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00723 Hom.: 10

Bravo AF: 0.00176

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs767845230; hg19: chr10-115469121;