Genetic Variant CASTOR1:c.*352G>T (chr22-30285268-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001037666.3(CASTOR1):c.*352G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000394 in 152,208 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000039 ( 0 hom., cov: 35)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CASTOR1
NM_001037666.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.843

Publications

17 publications found

Variant links:

Genes affected

CASTOR1 (HGNC:34423): (cytosolic arginine sensor for mTORC1 subunit 1) Enables arginine binding activity and identical protein binding activity. Involved in cellular response to L-arginine and negative regulation of TORC1 signaling. Located in cytosol. Colocalizes with GATOR2 complex. [provided by Alliance of Genome Resources, Apr 2022]

CASTOR1 links:

ENSG00000248751 (HGNC:):

ENSG00000248751 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037666.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASTOR1	NM_001037666.3	MANE Select	c.*352G>T		3_prime_UTR	Exon 9 of 9	NP_001032755.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CASTOR1	ENST00000407689.8	TSL:1 MANE Select	c.*352G>T	3_prime_UTR	Exon 9 of 9	ENSP00000384183.4
ENSG00000248751	ENST00000434291.5	TSL:2	c.*352G>T	3_prime_UTR	Exon 13 of 13	ENSP00000401535.1
CASTOR1	ENST00000865129.1		c.*352G>T	3_prime_UTR	Exon 9 of 9	ENSP00000535188.1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

52530

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

27478

African (AFR)

AF:

0.00

AC:

AN:

1730

American (AMR)

AF:

0.00

AC:

AN:

1132

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2076

East Asian (EAS)

AF:

0.00

AC:

AN:

3362

South Asian (SAS)

AF:

0.00

AC:

AN:

3476

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2728

Middle Eastern (MID)

AF:

0.00

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

34312

Other (OTH)

AF:

0.00

AC:

AN:

3442

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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.:

2381

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.7

(source)

DANN

Benign

0.28

PhyloP100

0.84

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over