rs2570467

Positions:

• chr5-96520975-A-G

Variant summary

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

The NM_001423250.1(CAST):​c.-175+141323A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,054 control chromosomes in the GnomAD database, including 7,173 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 0.29 (7173 hom., cov: 31)
• Consequence: CAST NM_001423250.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAST	NM_001423250.1	c.-175+141323A>G		intron_variant			NP_001410179.1
CAST	NM_001423251.1	c.-175+141323A>G		intron_variant			NP_001410180.1
CAST	NM_001423252.1	c.-175+141323A>G		intron_variant			NP_001410181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000251314	ENST00000502645.2	n.355-109992A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43732 AN: 151936 Hom.: 7172 Cov.: 31

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.288 AC: 43753 AN: 152054 Hom.: 7173 Cov.: 31 AF XY: 0.289 AC XY: 21479 AN XY: 74314

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.291

Alfa AF: 0.330 Hom.: 1475

Bravo AF: 0.271

Asia WGS AF: 0.219 AC: 760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2570467; hg19: chr5-95856679;