5-96662653-G-GGCAGGTGGCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001750.7(CAST):c.75+167_75+176dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (6951 hom., cov: 0)
• 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 Benign. Variant got -10 ACMG points.

• BP6: Variant 5-96662653-G-GGCAGGTGGCT is Benign according to our data. Variant chr5-96662653-G-GGCAGGTGGCT is described in ClinVar as [Benign]. Clinvar id is 1247631.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAST	NM_001750.7	c.75+167_75+176dup		intron_variant		ENST00000675179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAST	ENST00000675179.1	c.75+167_75+176dup		intron_variant			NM_001750.7	A2

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44346 AN: 151646 Hom.: 6943 Cov.: 0

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.292 AC: 44371 AN: 151758 Hom.: 6951 Cov.: 0 AF XY: 0.298 AC XY: 22081 AN XY: 74156

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.273

Alfa AF: 0.139 Hom.: 207

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

Jun 19, 2021

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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: rs80310955; hg19: chr5-95998357;