NM_001423250.1:c.-175+80075C>T

Variant names:

• chr5-96459727-C-T
• rs155974
• NM_001423250.1:c.-175+80075C>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001423250.1(CAST):​c.-175+80075C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0299 in 152,204 control chromosomes in the GnomAD database, including 216 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 0.030 (216 hom., cov: 32)
• Consequence: CAST NM_001423250.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAST	NM_001423250.1	c.-175+80075C>T		intron_variant	Intron 5 of 35		NP_001410179.1
CAST	NM_001423251.1	c.-175+80075C>T		intron_variant	Intron 5 of 34		NP_001410180.1
CAST	NM_001423252.1	c.-175+80075C>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+80075C>T		intron_variant	Intron 4 of 4	5

Frequencies

GnomAD3 genomes AF: 0.0299 AC: 4541 AN: 152086 Hom.: 217 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00727

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0172

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

GnomAD4 genome AF: 0.0299 AC: 4550 AN: 152204 Hom.: 216 Cov.: 32 AF XY: 0.0296 AC XY: 2207 AN XY: 74436

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.00726

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0171

Alfa AF: 0.0189 Hom.: 8

Bravo AF: 0.0324

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs155974; hg19: chr5-95795431;