5-96696123-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001750.7(CAST):c.210+216G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 308,498 control chromosomes in the GnomAD database, including 5,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2732 hom., cov: 32)
  • Exomes 𝑓: 0.20 (3070 hom.)
• Consequence: CAST NM_001750.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.264

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-96696123-G-T is Benign according to our data. Variant chr5-96696123-G-T is described in ClinVar as [Benign]. Clinvar id is 1282014.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAST	NM_001750.7	c.210+216G>T		intron_variant		ENST00000675179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAST	ENST00000675179.1	c.210+216G>T		intron_variant			NM_001750.7	A2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28299 AN: 151926 Hom.: 2729 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0870

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.195 AC: 30539 AN: 156452 Hom.: 3070 Cov.: 2 AF XY: 0.194 AC XY: 15576 AN XY: 80332

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.202

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.247

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.186 AC: 28306 AN: 152046 Hom.: 2732 Cov.: 32 AF XY: 0.190 AC XY: 14132 AN XY: 74312

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.173

Alfa AF: 0.199 Hom.: 386

Bravo AF: 0.178

Asia WGS AF: 0.256 AC: 890 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.3
Dann	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs42859; hg19: chr5-96031827;