5-96730948-C-T

Position:

• chr5-96730948-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.630+88C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 1,015,394 control chromosomes in the GnomAD database, including 261,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (35819 hom., cov: 32)
  • Exomes 𝑓: 0.72 (225822 hom.)
• Consequence: CAST NM_001750.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.293

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=-0.97).
• BP6: Variant 5-96730948-C-T is Benign according to our data. Variant chr5-96730948-C-T is described in ClinVar as [Benign]. Clinvar id is 1264261.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAST	NM_001750.7	c.630+88C>T		intron_variant		ENST00000675179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAST	ENST00000675179.1	c.630+88C>T		intron_variant			NM_001750.7	A2

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103730 AN: 151890 Hom.: 35790 Cov.: 32

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.673

GnomAD4 exome AF: 0.722 AC: 623268 AN: 863386 Hom.: 225822 AF XY: 0.719 AC XY: 324093 AN XY: 450890

Gnomad4 AFR exome AF: 0.575

Gnomad4 AMR exome AF: 0.838

Gnomad4 ASJ exome AF: 0.605

Gnomad4 EAS exome AF: 0.685

Gnomad4 SAS exome AF: 0.642

Gnomad4 FIN exome AF: 0.735

Gnomad4 NFE exome AF: 0.738

Gnomad4 OTH exome AF: 0.695

GnomAD4 genome AF: 0.683 AC: 103803 AN: 152008 Hom.: 35819 Cov.: 32 AF XY: 0.684 AC XY: 50811 AN XY: 74302

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.770

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.643

Gnomad4 SAS AF: 0.643

Gnomad4 FIN AF: 0.732

Gnomad4 NFE AF: 0.731

Gnomad4 OTH AF: 0.673

Alfa AF: 0.710 Hom.: 14975

Bravo AF: 0.683

Asia WGS AF: 0.665 AC: 2314 AN: 3478

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.7
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs151904; hg19: chr5-96066652; COSMIC: COSV57785468; COSMIC: COSV57785468;