Variant rs27654 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001750.7(CAST):c.1761+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,611,976 control chromosomes in the GnomAD database, including 96,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.36 ( 10341 hom., cov: 31)

Exomes 𝑓: 0.34 ( 86197 hom. )

Consequence

CAST
NM_001750.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.278

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 5-96757518-G-A is Benign according to our data. Variant chr5-96757518-G-A is described in ClinVar as [Benign]. Clinvar id is 1239061.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAST	NM_001750.7 linkuse as main transcript	c.1761+24G>A		intron_variant		ENST00000675179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAST	ENST00000675179.1 linkuse as main transcript	c.1761+24G>A		intron_variant			NM_001750.7	A2	P20810-6

Frequencies

GnomAD3 genomes

AF:

0.361

AC:

54834

AN:

151788

Hom.:

10316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.396

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.450

Gnomad ASJ

AF:

0.296

Gnomad EAS

AF:

0.512

Gnomad SAS

AF:

0.357

Gnomad FIN

AF:

0.359

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.316

Gnomad OTH

AF:

0.342

GnomAD3 exomes

AF:

0.378

AC:

94958

AN:

251262

Hom.:

19112

AF XY:

0.368

AC XY:

49998

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.399

Gnomad AMR exome

AF:

0.561

Gnomad ASJ exome

AF:

0.287

Gnomad EAS exome

AF:

0.477

Gnomad SAS exome

AF:

0.355

Gnomad FIN exome

AF:

0.363

Gnomad NFE exome

AF:

0.322

Gnomad OTH exome

AF:

0.351

GnomAD4 exome

AF:

0.337

AC:

491527

AN:

1460070

Hom.:

86197

Cov.:

AF XY:

0.336

AC XY:

244286

AN XY:

726478

show subpopulations

Gnomad4 AFR exome

AF:

0.400

Gnomad4 AMR exome

AF:

0.551

Gnomad4 ASJ exome

AF:

0.289

Gnomad4 EAS exome

AF:

0.563

Gnomad4 SAS exome

AF:

0.347

Gnomad4 FIN exome

AF:

0.370

Gnomad4 NFE exome

AF:

0.317

Gnomad4 OTH exome

AF:

0.336

GnomAD4 genome

AF:

0.361

AC:

54906

AN:

151906

Hom.:

10341

Cov.:

AF XY:

0.366

AC XY:

27163

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.397

Gnomad4 AMR

AF:

0.450

Gnomad4 ASJ

AF:

0.296

Gnomad4 EAS

AF:

0.512

Gnomad4 SAS

AF:

0.354

Gnomad4 FIN

AF:

0.359

Gnomad4 NFE

AF:

0.316

Gnomad4 OTH

AF:

0.344

Alfa

AF:

0.325

Hom.:

14567

Bravo

AF:

0.369

Asia WGS

AF:

0.451

AC:

1568

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.4

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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