5-96112290-C-T

Position:

• chr5-96112290-C-T

Variant summary

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

The NM_001423250.1(CAST):​c.-334+1285C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 152,090 control chromosomes in the GnomAD database, including 46,228 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 0.78 (46228 hom., cov: 31)
• Consequence: CAST NM_001423250.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428

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]

ENSG00000251314 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAST	NM_001423250.1	c.-334+1285C>T		intron_variant			NP_001410179.1
CAST	NM_001423251.1	c.-655+1285C>T		intron_variant			NP_001410180.1
CAST	NM_001423252.1	c.-334+1285C>T		intron_variant			NP_001410181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000251314	ENST00000502645.2	n.36+150254C>T		intron_variant		5
MIR583HG	ENST00000507997.1	n.159+1285C>T		intron_variant		2
ENSG00000251314	ENST00000511775.1	n.35+150254C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117787 AN: 151972 Hom.: 46190 Cov.: 31

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.775 AC: 117876 AN: 152090 Hom.: 46228 Cov.: 31 AF XY: 0.775 AC XY: 57629 AN XY: 74338

Gnomad4 AFR AF: 0.895

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.827

Gnomad4 NFE AF: 0.727

Gnomad4 OTH AF: 0.721

Alfa AF: 0.724 Hom.: 69163

Bravo AF: 0.767

Asia WGS AF: 0.788 AC: 2741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6865159; hg19: chr5-95447994;