5-96473535-A-C

Position:

• chr5-96473535-A-C

Variant summary

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

The NM_001423250.1(CAST):​c.-175+93883A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0729 in 152,290 control chromosomes in the GnomAD database, including 891 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 0.073 (891 hom., cov: 33)
• Consequence: CAST NM_001423250.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267

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]

LOC102724070 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAST	NM_001423250.1	c.-175+93883A>C		intron_variant			NP_001410179.1
CAST	NM_001423251.1	c.-175+93883A>C		intron_variant			NP_001410180.1
CAST	NM_001423252.1	c.-175+93883A>C		intron_variant			NP_001410181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000251314	ENST00000502645.2	n.354+93883A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0728 AC: 11074 AN: 152172 Hom.: 888 Cov.: 33

Gnomad AFR AF: 0.0512

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0977

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0400

Gnomad OTH AF: 0.0649

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

GnomAD4 genome AF: 0.0729 AC: 11095 AN: 152290 Hom.: 891 Cov.: 33 AF XY: 0.0795 AC XY: 5922 AN XY: 74456

Gnomad4 AFR AF: 0.0512

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.0369

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.0977

Gnomad4 NFE AF: 0.0400

Gnomad4 OTH AF: 0.0681

Alfa AF: 0.0487 Hom.: 442

Bravo AF: 0.0749

Asia WGS AF: 0.276 AC: 955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6860611; hg19: chr5-95809239;