5-96662687-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001750.7(CAST):c.75+190C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0565 in 111,632 control chromosomes in the GnomAD database, including 172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.057 (172 hom., cov: 32)
• Consequence: CAST NM_001750.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.08

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-96662687-C-T is Benign according to our data. Variant chr5-96662687-C-T is described in ClinVar as [Benign]. Clinvar id is 1247873.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAST	NM_001750.7	c.75+190C>T		intron_variant		ENST00000675179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAST	ENST00000675179.1	c.75+190C>T		intron_variant			NM_001750.7	A2

Frequencies

GnomAD3 genomes AF: 0.0566 AC: 6310 AN: 111576 Hom.: 173 Cov.: 32

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.0842

Gnomad AMR AF: 0.0642

Gnomad ASJ AF: 0.0577

Gnomad EAS AF: 0.000622

Gnomad SAS AF: 0.0213

Gnomad FIN AF: 0.0493

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.0739

Gnomad OTH AF: 0.0741

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

GnomAD4 genome AF: 0.0565 AC: 6310 AN: 111632 Hom.: 172 Cov.: 32 AF XY: 0.0564 AC XY: 3050 AN XY: 54066

Gnomad4 AFR AF: 0.0204

Gnomad4 AMR AF: 0.0641

Gnomad4 ASJ AF: 0.0577

Gnomad4 EAS AF: 0.000624

Gnomad4 SAS AF: 0.0219

Gnomad4 FIN AF: 0.0493

Gnomad4 NFE AF: 0.0740

Gnomad4 OTH AF: 0.0735

Alfa AF: 0.0517 Hom.: 36

Bravo AF: 0.0409

Asia WGS AF: 0.00809 AC: 28 AN: 3476

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 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.17
Dann	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs111620024; hg19: chr5-95998391;