5-96639598-C-T

Position:

• chr5-96639598-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000505143.5(CAST):​c.61-35941C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,004 control chromosomes in the GnomAD database, including 17,749 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (17749 hom., cov: 32)
• Consequence: CAST ENST00000505143.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAST	ENST00000505143.5	c.61-35941C>T		intron_variant		3		ENSP00000422957

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72407 AN: 151886 Hom.: 17743 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.477 AC: 72453 AN: 152004 Hom.: 17749 Cov.: 32 AF XY: 0.481 AC XY: 35751 AN XY: 74322

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.480

Alfa AF: 0.501 Hom.: 25623

Bravo AF: 0.458

Asia WGS AF: 0.519 AC: 1804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs155054; hg19: chr5-95975302;