22-30285268-C-G

Variant names:

• chr22-30285268-C-G
• rs1043099
• NM_001037666.3:c.*352G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001037666.3(CASTOR1):​c.*352G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.867 in 204,680 control chromosomes in the GnomAD database, including 77,471 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 0.87 (58624 hom., cov: 35)
  • Exomes 𝑓: 0.85 (18847 hom.)
• Consequence: CASTOR1 NM_001037666.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.843
• Publications: 17 publications found

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]

ENSG00000248751 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.875 AC: 133099 AN: 152184 Hom.: 58566 Cov.: 35

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.907

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.877

GnomAD4 exome AF: 0.846 AC: 44306 AN: 52378 Hom.: 18847 Cov.: 0 AF XY: 0.848 AC XY: 23236 AN XY: 27400

African (AFR) AF: 0.970 AC: 1674 AN: 1726

American (AMR) AF: 0.874 AC: 986 AN: 1128

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 1847 AN: 2074

East Asian (EAS) AF: 0.917 AC: 3079 AN: 3358

South Asian (SAS) AF: 0.913 AC: 3171 AN: 3474

European-Finnish (FIN) AF: 0.874 AC: 2375 AN: 2716

Middle Eastern (MID) AF: 0.945 AC: 257 AN: 272

European-Non Finnish (NFE) AF: 0.817 AC: 27954 AN: 34196

Other (OTH) AF: 0.863 AC: 2963 AN: 3434

GnomAD4 genome AF: 0.875 AC: 133214 AN: 152302 Hom.: 58624 Cov.: 35 AF XY: 0.879 AC XY: 65487 AN XY: 74466

African (AFR) AF: 0.967 AC: 40193 AN: 41576

American (AMR) AF: 0.872 AC: 13342 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.892 AC: 3098 AN: 3472

East Asian (EAS) AF: 0.905 AC: 4674 AN: 5166

South Asian (SAS) AF: 0.906 AC: 4380 AN: 4832

European-Finnish (FIN) AF: 0.888 AC: 9422 AN: 10616

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55303 AN: 68010

Other (OTH) AF: 0.879 AC: 1860 AN: 2116

Alfa AF: 0.789 Hom.: 2381

Bravo AF: 0.875

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.40
PhyloP100		0.84
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1043099; hg19: chr22-30681257;