Variant 5-96695865-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001750.7(CAST):c.168A>G(p.Gln56Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,608,786 control chromosomes in the GnomAD database, including 34,189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2742 hom., cov: 31)

Exomes 𝑓: 0.20 ( 31447 hom. )

Consequence

CAST
NM_001750.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.01

Variant links:

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]

CAST links:

CAST (HGNC:):

CAST links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 5-96695865-A-G is Benign according to our data. Variant chr5-96695865-A-G is described in ClinVar as [Benign]. Clinvar id is 1192696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAST	NM_001750.7 linkuse as main transcript	c.168A>G	p.Gln56Gln	synonymous_variant	3/32	ENST00000675179.1	NP_001741.4	P20810-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAST	ENST00000675179.1 linkuse as main transcript	c.168A>G	p.Gln56Gln	synonymous_variant	3/32		NM_001750.7	ENSP00000501872.1		P20810-6

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28353

AN:

151990

Hom.:

2739

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.209

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.202

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.211

AC:

52378

AN:

247922

Hom.:

5775

AF XY:

0.212

AC XY:

28463

AN XY:

134504

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.230

Gnomad ASJ exome

AF:

0.132

Gnomad EAS exome

AF:

0.236

Gnomad SAS exome

AF:

0.224

Gnomad FIN exome

AF:

0.254

Gnomad NFE exome

AF:

0.209

Gnomad OTH exome

AF:

0.200

GnomAD4 exome

AF:

0.205

AC:

298314

AN:

1456678

Hom.:

31447

Cov.:

AF XY:

0.206

AC XY:

149102

AN XY:

724680

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.232

Gnomad4 ASJ exome

AF:

0.135

Gnomad4 EAS exome

AF:

0.261

Gnomad4 SAS exome

AF:

0.221

Gnomad4 FIN exome

AF:

0.254

Gnomad4 NFE exome

AF:

0.203

Gnomad4 OTH exome

AF:

0.196

GnomAD4 genome

AF:

0.186

AC:

28360

AN:

152108

Hom.:

2742

Cov.:

AF XY:

0.190

AC XY:

14144

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.132

Gnomad4 AMR

AF:

0.210

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.234

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.257

Gnomad4 NFE

AF:

0.202

Gnomad4 OTH

AF:

0.173

Alfa

AF:

0.199

Hom.:

6186

Bravo

AF:

0.179

Asia WGS

AF:

0.259

AC:

901

AN:

3478

EpiCase

AF:

0.198

EpiControl

AF:

0.193

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.1

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over