5-96760515-C-G

Variant names:

• chr5-96760515-C-G
• rs7711564
• NM_001750.7:c.1834-1759C>G

Variant summary

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

The NM_001750.7(CAST):​c.1834-1759C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 151,722 control chromosomes in the GnomAD database, including 6,834 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 (6834 hom., cov: 33)
• Consequence: CAST NM_001750.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.969

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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAST	NM_001750.7	c.1834-1759C>G		intron_variant	Intron 24 of 31	ENST00000675179.1	NP_001741.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAST	ENST00000675179.1	c.1834-1759C>G		intron_variant	Intron 24 of 31		NM_001750.7	ENSP00000501872.1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43773 AN: 151600 Hom.: 6821 Cov.: 33

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.289 AC: 43824 AN: 151722 Hom.: 6834 Cov.: 33 AF XY: 0.295 AC XY: 21840 AN XY: 74100

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.280

Alfa AF: 0.278 Hom.: 758

Bravo AF: 0.295

Asia WGS AF: 0.412 AC: 1417 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.9
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7711564; hg19: chr5-96096219;