rs6860611

Variant names:

• chr5-96473535-A-C
• rs6860611

Your query was ambiguous. Multiple possible variants found:

• chr5-96473535-A-C
• chr5-96473535-A-G

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 0.0729 in 152,290 control chromosomes in the GnomAD database, including 891 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 0.073 (891 hom., cov: 33)
• Consequence: LOC102724070 intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000718093.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAST	NM_001423250.1		c.-175+93883A>C		intron	N/A	NP_001410179.1
	CAST	NM_001423251.1		c.-175+93883A>C		intron	N/A	NP_001410180.1
	CAST	NM_001423252.1		c.-175+93883A>C		intron	N/A	NP_001410181.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAST	ENST00000718093.1		c.-175+93883A>C		intron	N/A	ENSP00000520668.1
	CAST	ENST00000718091.1		c.-175+93883A>C		intron	N/A	ENSP00000520667.1
	CAST	ENST00000718090.1		n.240+93883A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0728 AC: 11074 AN: 152172 Hom.: 888 Cov.: 33

Gnomad AFR AF: 0.0512

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0977

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0400

Gnomad OTH AF: 0.0649

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

GnomAD4 genome AF: 0.0729 AC: 11095 AN: 152290 Hom.: 891 Cov.: 33 AF XY: 0.0795 AC XY: 5922 AN XY: 74456

African (AFR) AF: 0.0512 AC: 2127 AN: 41568

American (AMR) AF: 0.132 AC: 2021 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0369 AC: 128 AN: 3470

East Asian (EAS) AF: 0.413 AC: 2136 AN: 5172

South Asian (SAS) AF: 0.148 AC: 712 AN: 4822

European-Finnish (FIN) AF: 0.0977 AC: 1037 AN: 10612

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0400 AC: 2723 AN: 68026

Other (OTH) AF: 0.0681 AC: 144 AN: 2116

Alfa AF: 0.0496 Hom.: 528

Bravo AF: 0.0749

Asia WGS AF: 0.276 AC: 955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.58
PhyloP100		-0.27

Splicing

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

Other links and lift over

dbSNP: rs6860611; hg19: chr5-95809239;