Variant rs10515244 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.1099-22C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,505,340 control chromosomes in the GnomAD database, including 11,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.094 ( 883 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10656 hom. )

Consequence

CAST
NM_001750.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.374

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:

(HGNC:):

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=-0.66).

BP6

Variant 5-96742633-C-G is Benign according to our data. Variant chr5-96742633-C-G is described in ClinVar as [Benign]. Clinvar id is 1221320.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.134 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.1099-22C>G		intron_variant		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.1099-22C>G		intron_variant			NM_001750.7	ENSP00000501872	A2	P20810-6
	ENST00000502568.1 linkuse as main transcript	n.66G>C		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

AF:

0.0942

AC:

14319

AN:

152026

Hom.:

882

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0230

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.000964

Gnomad SAS

AF:

0.0780

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.123

GnomAD3 exomes

AF:

0.102

AC:

25358

AN:

248328

Hom.:

1587

AF XY:

0.105

AC XY:

14093

AN XY:

134230

show subpopulations

Gnomad AFR exome

AF:

0.0219

Gnomad AMR exome

AF:

0.0697

Gnomad ASJ exome

AF:

0.117

Gnomad EAS exome

AF:

0.00132

Gnomad SAS exome

AF:

0.0727

Gnomad FIN exome

AF:

0.129

Gnomad NFE exome

AF:

0.140

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.120

AC:

162912

AN:

1353194

Hom.:

10656

Cov.:

AF XY:

0.120

AC XY:

81475

AN XY:

679548

show subpopulations

Gnomad4 AFR exome

AF:

0.0209

Gnomad4 AMR exome

AF:

0.0738

Gnomad4 ASJ exome

AF:

0.114

Gnomad4 EAS exome

AF:

0.000741

Gnomad4 SAS exome

AF:

0.0756

Gnomad4 FIN exome

AF:

0.129

Gnomad4 NFE exome

AF:

0.134

Gnomad4 OTH exome

AF:

0.110

GnomAD4 genome

AF:

0.0941

AC:

14319

AN:

152146

Hom.:

883

Cov.:

AF XY:

0.0941

AC XY:

6999

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0229

Gnomad4 AMR

AF:

0.101

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.000966

Gnomad4 SAS

AF:

0.0785

Gnomad4 FIN

AF:

0.133

Gnomad4 NFE

AF:

0.136

Gnomad4 OTH

AF:

0.122

Alfa

AF:

0.113

Hom.:

185

Bravo

AF:

0.0888

Asia WGS

AF:

0.0320

AC:

112

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

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.0

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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