rs2276015

chr11-65976832-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005146.5(SART1):c.1857+66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00704 in 1,381,676 control chromosomes in the GnomAD database, including 562 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 0.014 (79 hom., cov: 33)
  • Exomes 𝑓: 0.0061 (483 hom.)
• Consequence: SART1 NM_005146.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223

Genes affected

SART1 (HGNC:10538): (spliceosome associated factor 1, recruiter of U4/U6.U5 tri-snRNP) This gene encodes two proteins, the SART1(800) protein expressed in the nucleus of the majority of proliferating cells, and the SART1(259) protein expressed in the cytosol of epithelial cancers. The SART1(259) protein is translated by the mechanism of -1 frameshifting during posttranscriptional regulation; its full-length sequence is not published yet. The two encoded proteins are thought to be involved in the regulation of proliferation. Both proteins have tumor-rejection antigens. The SART1(259) protein possesses tumor epitopes capable of inducing HLA-A2402-restricted cytotoxic T lymphocytes in cancer patients. This SART1(259) antigen may be useful in specific immunotherapy for cancer patients and may serve as a paradigmatic tool for the diagnosis and treatment of patients with atopy. The SART1(259) protein is found to be essential for the recruitment of the tri-snRNP to the pre-spliceosome in the spliceosome assembly pathway. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SART1	NM_005146.5	c.1857+66C>T		intron_variant		ENST00000312397.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SART1	ENST00000312397.10	c.1857+66C>T		intron_variant		1	NM_005146.5	P1
SART1	ENST00000533386.1	n.18+66C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2174 AN: 152150 Hom.: 78 Cov.: 33

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.00766

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0124

GnomAD4 exome AF: 0.00613 AC: 7542 AN: 1229408 Hom.: 483 Cov.: 17 AF XY: 0.00595 AC XY: 3646 AN XY: 612606

Gnomad4 AFR exome AF: 0.0269

Gnomad4 AMR exome AF: 0.0112

Gnomad4 ASJ exome AF: 0.00195

Gnomad4 EAS exome AF: 0.153

Gnomad4 SAS exome AF: 0.00400

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000103

Gnomad4 OTH exome AF: 0.0104

GnomAD4 genome AF: 0.0143 AC: 2185 AN: 152268 Hom.: 79 Cov.: 33 AF XY: 0.0159 AC XY: 1185 AN XY: 74448

Gnomad4 AFR AF: 0.0251

Gnomad4 AMR AF: 0.0165

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.00808

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.00403 Hom.: 3

Bravo AF: 0.0168

Asia WGS AF: 0.0520 AC: 180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	6.3
Dann	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs2276015; hg19: chr11-65744303; COSMIC: COSV56714024; COSMIC: COSV56714024;