5-96662653-G-GGCAGGTGGCAGCAGGTGGCT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001750.7(CAST):c.75+165_75+166insAGCAGGTGGCTGCAGGTGGC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (8284 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: CAST NM_001750.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.132

Genes affected

CAST (HGNC:1515): (calpastatin) The protein encoded by this gene is an endogenous calpain (calcium-dependent cysteine protease) inhibitor. It consists of an N-terminal domain L and four repetitive calpain-inhibition domains (domains 1-4), and it is involved in the proteolysis of amyloid precursor protein. The calpain/calpastatin system is involved in numerous membrane fusion events, such as neural vesicle exocytosis and platelet and red-cell aggregation. The encoded protein is also thought to affect the expression levels of genes encoding structural or regulatory proteins. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 5-96662653-G-GGCAGGTGGCAGCAGGTGGCT is Benign according to our data. Variant chr5-96662653-G-GGCAGGTGGCAGCAGGTGGCT is described in ClinVar as [Benign]. Clinvar id is 1274367.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAST	NM_001750.7	c.75+165_75+166insAGCAGGTGGCTGCAGGTGGC		intron_variant		ENST00000675179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAST	ENST00000675179.1	c.75+165_75+166insAGCAGGTGGCTGCAGGTGGC		intron_variant			NM_001750.7	A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 45722 AN: 151612 Hom.: 8268 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.296

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.302 AC: 45772 AN: 151724 Hom.: 8284 Cov.: 0 AF XY: 0.300 AC XY: 22253 AN XY: 74136

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.298

Alfa AF: 0.0882 Hom.: 86

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs146973537; hg19: chr5-95998357;