Variant 5-96634450-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001423250.1(CAST):c.-174-41089T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 152,092 control chromosomes in the GnomAD database, including 37,805 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 0.70 ( 37805 hom., cov: 32)

Consequence

CAST
NM_001423250.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.186

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 -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein
CAST	NM_001423250.1 link	c.-174-41089T>G	intron_variant	NP_001410179.1
CAST	NM_001423251.1 link	c.-174-41089T>G	intron_variant	NP_001410180.1
CAST	NM_001423252.1 link	c.-174-41089T>G	intron_variant	NP_001410181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAST	ENST00000505143.5 link	c.61-41089T>G		intron_variant		3		ENSP00000422957.2		H0Y944

Frequencies

GnomAD3 genomes

AF:

0.695

AC:

105667

AN:

151974

Hom.:

37761

Cov.:

show subpopulations

Gnomad AFR

AF:

0.861

Gnomad AMI

AF:

0.623

Gnomad AMR

AF:

0.593

Gnomad ASJ

AF:

0.568

Gnomad EAS

AF:

0.796

Gnomad SAS

AF:

0.622

Gnomad FIN

AF:

0.688

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.624

Gnomad OTH

AF:

0.683

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

GnomAD4 genome

AF:

0.695

AC:

105760

AN:

152092

Hom.:

37805

Cov.:

AF XY:

0.696

AC XY:

51722

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.862

Gnomad4 AMR

AF:

0.592

Gnomad4 ASJ

AF:

0.568

Gnomad4 EAS

AF:

0.797

Gnomad4 SAS

AF:

0.621

Gnomad4 FIN

AF:

0.688

Gnomad4 NFE

AF:

0.624

Gnomad4 OTH

AF:

0.682

Alfa

AF:

0.646

Hom.:

15169

Bravo

AF:

0.697

Asia WGS

AF:

0.682

AC:

2369

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.1

DANN

Benign

0.73

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over