Variant rs7724759 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001750.7(CAST):c.918G>A(p.Ser306=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,575,622 control chromosomes in the GnomAD database, including 70,217 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4989 hom., cov: 32)

Exomes 𝑓: 0.29 ( 65228 hom. )

Consequence

CAST
NM_001750.7 splice_region, synonymous

Scores

Splicing: ADA: 0.9955

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.08

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 5-96740783-G-A is Benign according to our data. Variant chr5-96740783-G-A is described in ClinVar as [Benign]. Clinvar id is 1274351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 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.918G>A	p.Ser306=	splice_region_variant, synonymous_variant	13/32	ENST00000675179.1	NP_001741.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAST	ENST00000675179.1 linkuse as main transcript	c.918G>A	p.Ser306=	splice_region_variant, synonymous_variant	13/32		NM_001750.7	ENSP00000501872	A2	P20810-6

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

35971

AN:

151908

Hom.:

4987

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.318

Gnomad AMR

AF:

0.217

Gnomad ASJ

AF:

0.305

Gnomad EAS

AF:

0.0742

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.275

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.323

Gnomad OTH

AF:

0.249

GnomAD3 exomes

AF:

0.248

AC:

62042

AN:

250004

Hom.:

8727

AF XY:

0.256

AC XY:

34573

AN XY:

135170

show subpopulations

Gnomad AFR exome

AF:

0.104

Gnomad AMR exome

AF:

0.175

Gnomad ASJ exome

AF:

0.305

Gnomad EAS exome

AF:

0.0802

Gnomad SAS exome

AF:

0.230

Gnomad FIN exome

AF:

0.274

Gnomad NFE exome

AF:

0.312

Gnomad OTH exome

AF:

0.276

GnomAD4 exome

AF:

0.293

AC:

417564

AN:

1423596

Hom.:

65228

Cov.:

AF XY:

0.293

AC XY:

208330

AN XY:

710198

show subpopulations

Gnomad4 AFR exome

AF:

0.101

Gnomad4 AMR exome

AF:

0.176

Gnomad4 ASJ exome

AF:

0.304

Gnomad4 EAS exome

AF:

0.0762

Gnomad4 SAS exome

AF:

0.231

Gnomad4 FIN exome

AF:

0.269

Gnomad4 NFE exome

AF:

0.319

Gnomad4 OTH exome

AF:

0.281

GnomAD4 genome

AF:

0.237

AC:

35984

AN:

152026

Hom.:

4989

Cov.:

AF XY:

0.233

AC XY:

17301

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.107

Gnomad4 AMR

AF:

0.217

Gnomad4 ASJ

AF:

0.305

Gnomad4 EAS

AF:

0.0744

Gnomad4 SAS

AF:

0.217

Gnomad4 FIN

AF:

0.275

Gnomad4 NFE

AF:

0.323

Gnomad4 OTH

AF:

0.252

Alfa

AF:

0.295

Hom.:

12430

Bravo

AF:

0.227

Asia WGS

AF:

0.167

AC:

578

AN:

3478

EpiCase

AF:

0.320

EpiControl

AF:

0.325

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	This variant is associated with the following publications: (PMID: 20011102, 17671095) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

3.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.84

SpliceAI score (max)

0.32

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.32

Position offset: 0

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