5-96746697-C-T

Position:

• chr5-96746697-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.1284+272C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.919 in 152,290 control chromosomes in the GnomAD database, including 64,393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.92 (64393 hom., cov: 33)
• Consequence: CAST NM_001750.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.450

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=-0.93).
• BP6: Variant 5-96746697-C-T is Benign according to our data. Variant chr5-96746697-C-T is described in ClinVar as [Benign]. Clinvar id is 1249890.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAST	NM_001750.7	c.1284+272C>T		intron_variant		ENST00000675179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAST	ENST00000675179.1	c.1284+272C>T		intron_variant			NM_001750.7	A2

Frequencies

GnomAD3 genomes AF: 0.919 AC: 139805 AN: 152172 Hom.: 64354 Cov.: 33

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.971

Gnomad AMR AF: 0.949

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.901

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.940

Gnomad OTH AF: 0.931

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

GnomAD4 genome AF: 0.919 AC: 139897 AN: 152290 Hom.: 64393 Cov.: 33 AF XY: 0.921 AC XY: 68554 AN XY: 74466

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.949

Gnomad4 ASJ AF: 0.886

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.902

Gnomad4 FIN AF: 0.956

Gnomad4 NFE AF: 0.940

Gnomad4 OTH AF: 0.932

Alfa AF: 0.926 Hom.: 30873

Bravo AF: 0.915

Asia WGS AF: 0.957 AC: 3327 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	-0.93
CADD	Benign	7.0
DANN	Benign	0.62

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: rs27851; hg19: chr5-96082401;