chr5-96435158-C-T

Variant names:

• chr5-96435158-C-T
• rs3762986
• NM_001423250.1:c.-175+55506C>T

Variant summary

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

The NM_001423250.1(CAST):​c.-175+55506C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 151,986 control chromosomes in the GnomAD database, including 19,227 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 0.50 (19227 hom., cov: 32)
• Consequence: CAST NM_001423250.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAST	NM_001423250.1	c.-175+55506C>T		intron_variant	Intron 5 of 35		NP_001410179.1
CAST	NM_001423251.1	c.-175+55506C>T		intron_variant	Intron 5 of 34		NP_001410180.1
CAST	NM_001423252.1	c.-175+55506C>T		intron_variant	Intron 4 of 33		NP_001410181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000251314	ENST00000502645.2	n.354+55506C>T		intron_variant	Intron 4 of 4	5

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75491 AN: 151868 Hom.: 19202 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.497 AC: 75561 AN: 151986 Hom.: 19227 Cov.: 32 AF XY: 0.503 AC XY: 37359 AN XY: 74292

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.521

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.565

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.457

Alfa AF: 0.441 Hom.: 20055

Bravo AF: 0.489

Asia WGS AF: 0.529 AC: 1843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3762986; hg19: chr5-95770862;