rs152005

chr5-96690143-A-G

Variant summary

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

The NM_001750.7(CAST):c.139-5693A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,154 control chromosomes in the GnomAD database, including 3,315 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 0.20 (3315 hom., cov: 32)
• Consequence: CAST NM_001750.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAST	NM_001750.7	c.139-5693A>G		intron_variant		ENST00000675179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAST	ENST00000675179.1	c.139-5693A>G		intron_variant			NM_001750.7	A2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29814 AN: 152036 Hom.: 3307 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.196 AC: 29846 AN: 152154 Hom.: 3315 Cov.: 32 AF XY: 0.197 AC XY: 14665 AN XY: 74370

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.199

Alfa AF: 0.164 Hom.: 2358

Bravo AF: 0.197

Asia WGS AF: 0.268 AC: 931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.1
Dann	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs152005; hg19: chr5-96025847;