5-96435158-C-T

Variant names:

• chr5-96435158-C-T
• rs3762986

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.497 in 151,986 control chromosomes in the GnomAD database, including 19,227 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 0.50 (19227 hom., cov: 32)
• Consequence: LOC102724070 intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370
• Publications: 9 publications found

Genes affected

LOC102724070 (HGNC:):

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]

CAST Gene-Disease associations (from GenCC):

• peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC102724070		n.96435158C>T		intragenic_variant
CAST	NM_001423250.1	c.-175+55506C>T		intron_variant	Intron 5 of 35		NP_001410179.1
CAST	NM_001423251.1	c.-175+55506C>T		intron_variant	Intron 5 of 34		NP_001410180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAST	ENST00000718093.1	c.-175+55506C>T		intron_variant	Intron 3 of 30			ENSP00000520668.1
CAST	ENST00000718091.1	c.-175+55506C>T		intron_variant	Intron 3 of 11			ENSP00000520667.1
CAST	ENST00000718089.1	n.450-6737C>T		intron_variant	Intron 5 of 6
CAST	ENST00000718090.1	n.240+55506C>T		intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75491 AN: 151868 Hom.: 19202 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.497 AC: 75561 AN: 151986 Hom.: 19227 Cov.: 32 AF XY: 0.503 AC XY: 37359 AN XY: 74292

African (AFR) AF: 0.590 AC: 24431 AN: 41436

American (AMR) AF: 0.416 AC: 6354 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1607 AN: 3472

East Asian (EAS) AF: 0.521 AC: 2693 AN: 5164

South Asian (SAS) AF: 0.546 AC: 2629 AN: 4814

European-Finnish (FIN) AF: 0.565 AC: 5960 AN: 10542

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30274 AN: 67952

Other (OTH) AF: 0.457 AC: 965 AN: 2112

Alfa AF: 0.447 Hom.: 26111

Bravo AF: 0.489

Asia WGS AF: 0.529 AC: 1843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.68
PhyloP100		0.037

Splicing

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

Other links and lift over

dbSNP: rs3762986; hg19: chr5-95770862;