rs59338324

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001750.7(CAST):c.2037+14_2037+28delAAAAAAAAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 512,284 control chromosomes in the GnomAD database, including 5 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00025 ( 5 hom. )

Consequence

CAST
NM_001750.7 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.47

Publications

1 publications found

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:

ERAP1 (HGNC:18173): (endoplasmic reticulum aminopeptidase 1) The protein encoded by this gene is an aminopeptidase involved in trimming HLA class I-binding precursors so that they can be presented on MHC class I molecules. The encoded protein acts as a monomer or as a heterodimer with ERAP2. This protein may also be involved in blood pressure regulation by inactivation of angiotensin II. Three transcript variants encoding two different isoforms have been found for this gene.[provided by RefSeq, Oct 2010]

ERAP1 links:

CAST (HGNC:):

CAST links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 5-96765327-TAAAAAAAAAAAAAAA-T is Benign according to our data. Variant chr5-96765327-TAAAAAAAAAAAAAAA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2987448.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000162 (16/98894) while in subpopulation EAS AF = 0.00469 (16/3408). AF 95% confidence interval is 0.00294. There are 0 homozygotes in GnomAd4. There are 7 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001750.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CAST	NM_001750.7	MANE Select	c.2037+14_2037+28delAAAAAAAAAAAAAAA	intron	N/A	NP_001741.4
ERAP1	NM_001349244.2		c.2819-2114_2819-2100delTTTTTTTTTTTTTTT	intron	N/A	NP_001336173.1
ERAP1	NM_016442.5		c.2819-2114_2819-2100delTTTTTTTTTTTTTTT	intron	N/A	NP_057526.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CAST	ENST00000675179.1	MANE Select	c.2037+3_2037+17delAAAAAAAAAAAAAAA	splice_region intron	N/A	ENSP00000501872.1
ERAP1	ENST00000296754.7	TSL:1	c.2819-2114_2819-2100delTTTTTTTTTTTTTTT	intron	N/A	ENSP00000296754.3
CAST	ENST00000341926.7	TSL:1	c.1788+3_1788+17delAAAAAAAAAAAAAAA	splice_region intron	N/A	ENSP00000339914.3

Frequencies

GnomAD3 genomes

AF:

0.000162

AC:

AN:

98902

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00467

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000252

AC:

104

AN:

413390

Hom.:

AF XY:

0.000256

AC XY:

AN XY:

222584

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

9286

American (AMR)

AF:

0.00

AC:

AN:

13674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11092

East Asian (EAS)

AF:

0.00444

AC:

103

AN:

23220

South Asian (SAS)

AF:

0.00

AC:

AN:

30870

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30536

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1706

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

271036

Other (OTH)

AF:

0.0000455

AC:

AN:

21970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.639

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000162

AC:

AN:

98894

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

AN XY:

45260

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25358

American (AMR)

AF:

0.00

AC:

AN:

9092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2730

East Asian (EAS)

AF:

0.00469

AC:

AN:

3408

South Asian (SAS)

AF:

0.00

AC:

AN:

2876

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2698

Middle Eastern (MID)

AF:

0.00

AC:

AN:

164

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

50520

Other (OTH)

AF:

0.00

AC:

AN:

1312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.681

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.5

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over