rs27852

chr5-96710335-A-Cchr5-96710335-A-Gchr5-96710335-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.211-12304A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 151,906 control chromosomes in the GnomAD database, including 31,726 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 0.64 (31726 hom., cov: 31)
• Consequence: CAST NM_001750.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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]

LOC107986363 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAST	NM_001750.7	c.211-12304A>C		intron_variant		ENST00000675179.1
LOC107986363	XR_001742454.2	n.4991A>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAST	ENST00000675179.1	c.211-12304A>C		intron_variant			NM_001750.7	A2

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97425 AN: 151788 Hom.: 31699 Cov.: 31

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.692

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.642 AC: 97494 AN: 151906 Hom.: 31726 Cov.: 31 AF XY: 0.639 AC XY: 47458 AN XY: 74216

Gnomad4 AFR AF: 0.564

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.666

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.658

Alfa AF: 0.688 Hom.: 45747

Bravo AF: 0.636

Asia WGS AF: 0.560 AC: 1950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.21
Dann	Benign	0.38

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: rs27852; hg19: chr5-96046039;