rs1862182

chr5-96663822-A-Gchr5-96663822-A-T

Variant summary

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

The NM_001750.7(CAST):c.75+1325A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 151,990 control chromosomes in the GnomAD database, including 52,627 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 0.83 (52627 hom., cov: 29)
• Consequence: CAST NM_001750.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAST	NM_001750.7	c.75+1325A>G		intron_variant		ENST00000675179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAST	ENST00000675179.1	c.75+1325A>G		intron_variant			NM_001750.7	A2

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125464 AN: 151872 Hom.: 52561 Cov.: 29

Gnomad AFR AF: 0.957

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.790

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

GnomAD4 genome AF: 0.826 AC: 125594 AN: 151990 Hom.: 52627 Cov.: 29 AF XY: 0.828 AC XY: 61479 AN XY: 74246

Gnomad4 AFR AF: 0.957

Gnomad4 AMR AF: 0.852

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.784

Gnomad4 FIN AF: 0.763

Gnomad4 NFE AF: 0.752

Gnomad4 OTH AF: 0.792

Alfa AF: 0.756 Hom.: 55162

Bravo AF: 0.838

Asia WGS AF: 0.902 AC: 3136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	6.7
Dann	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1862182; hg19: chr5-95999526;