rs2234975

Positions:

• chr10-67918321-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4 BA1

The NM_012238.5(SIRT1):​c.*1728C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0584 in 152,590 control chromosomes in the GnomAD database, including 342 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 0.058 (341 hom., cov: 33)
  • Exomes 𝑓: 0.074 (1 hom.)
• Consequence: SIRT1 NM_012238.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.85

Genes affected

SIRT1 (HGNC:14929): (sirtuin 1) This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the sirtuin family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.15).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRT1	NM_012238.5	c.*1728C>T		3_prime_UTR_variant	9/9	ENST00000212015.11
SIRT1	NM_001142498.2	c.*1728C>T		3_prime_UTR_variant	8/8
SIRT1	NM_001314049.2	c.*1728C>T		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRT1	ENST00000212015.11	c.*1728C>T		3_prime_UTR_variant	9/9	1	NM_012238.5	P1
SIRT1	ENST00000403579.1	c.*1728C>T		3_prime_UTR_variant	6/6	1
SIRT1	ENST00000406900.5	c.*1728C>T		3_prime_UTR_variant	7/7	2
SIRT1	ENST00000432464.5	c.*1728C>T		3_prime_UTR_variant	8/8	5

Frequencies

GnomAD3 genomes AF: 0.0584 AC: 8873 AN: 152040 Hom.: 340 Cov.: 33

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0667

Gnomad ASJ AF: 0.0948

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0190

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0857

Gnomad OTH AF: 0.0736

GnomAD4 exome AF: 0.0741 AC: 32 AN: 432 Hom.: 1 Cov.: 0 AF XY: 0.0923 AC XY: 24 AN XY: 260

Gnomad4 FIN exome AF: 0.0751

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0583 AC: 8872 AN: 152158 Hom.: 341 Cov.: 33 AF XY: 0.0556 AC XY: 4139 AN XY: 74380

Gnomad4 AFR AF: 0.0160

Gnomad4 AMR AF: 0.0666

Gnomad4 ASJ AF: 0.0948

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0189

Gnomad4 FIN AF: 0.0694

Gnomad4 NFE AF: 0.0857

Gnomad4 OTH AF: 0.0728

Alfa AF: 0.0750 Hom.: 133

Bravo AF: 0.0571

Asia WGS AF: 0.00982 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
CADD	Benign	19
DANN	Benign	0.89

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: rs2234975; hg19: chr10-69678078;