5-96478962-G-A

Variant names:

• chr5-96478962-G-A
• rs155437

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 0.509 in 152,084 control chromosomes in the GnomAD database, including 20,158 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 0.51 (20158 hom., cov: 33)
• Consequence: LOC102724070 intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• Publications: 5 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 (AFR) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC102724070		n.96478962G>A		intragenic_variant
CAST	NM_001423250.1	c.-175+99310G>A		intron_variant	Intron 5 of 35		NP_001410179.1
CAST	NM_001423251.1	c.-175+99310G>A		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+99310G>A		intron_variant	Intron 3 of 30			ENSP00000520668.1
CAST	ENST00000718091.1	c.-175+99310G>A		intron_variant	Intron 3 of 11			ENSP00000520667.1
CAST	ENST00000718090.1	n.240+99310G>A		intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77320 AN: 151966 Hom.: 20121 Cov.: 33

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.509 AC: 77405 AN: 152084 Hom.: 20158 Cov.: 33 AF XY: 0.503 AC XY: 37365 AN XY: 74348

African (AFR) AF: 0.620 AC: 25718 AN: 41502

American (AMR) AF: 0.467 AC: 7132 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1128 AN: 3468

East Asian (EAS) AF: 0.484 AC: 2498 AN: 5166

South Asian (SAS) AF: 0.348 AC: 1678 AN: 4822

European-Finnish (FIN) AF: 0.454 AC: 4808 AN: 10580

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32879 AN: 67968

Other (OTH) AF: 0.492 AC: 1039 AN: 2112

Alfa AF: 0.488 Hom.: 56016

Bravo AF: 0.512

Asia WGS AF: 0.442 AC: 1535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.63
PhyloP100		-0.12

Splicing

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

Other links and lift over

dbSNP: rs155437; hg19: chr5-95814666;