rs3740053

Variant names:

• chr10-67884577-A-G
• rs3740053
• NM_012238.5:c.-145A>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_012238.5(SIRT1):​c.-145A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0761 in 945,574 control chromosomes in the GnomAD database, including 4,095 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 0.076 (727 hom., cov: 35)
  • Exomes 𝑓: 0.076 (3368 hom.)
• Consequence: SIRT1 NM_012238.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT1	NM_012238.5	c.-145A>G		upstream_gene_variant		ENST00000212015.11	NP_036370.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT1	ENST00000212015.11	c.-145A>G		upstream_gene_variant		1	NM_012238.5	ENSP00000212015.6

Frequencies

GnomAD3 genomes AF: 0.0760 AC: 11558 AN: 152032 Hom.: 726 Cov.: 35

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.0727

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0406

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0659

Gnomad OTH AF: 0.0745

GnomAD4 exome AF: 0.0762 AC: 60447 AN: 793424 Hom.: 3368 AF XY: 0.0758 AC XY: 28859 AN XY: 380606

Gnomad4 AFR exome AF: 0.0238

Gnomad4 AMR exome AF: 0.148

Gnomad4 ASJ exome AF: 0.0460

Gnomad4 EAS exome AF: 0.320

Gnomad4 SAS exome AF: 0.134

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.0650

Gnomad4 OTH exome AF: 0.0816

GnomAD4 genome AF: 0.0760 AC: 11556 AN: 152150 Hom.: 727 Cov.: 35 AF XY: 0.0819 AC XY: 6094 AN XY: 74394

Gnomad4 AFR AF: 0.0268

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.0406

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.0659

Gnomad4 OTH AF: 0.0733

Alfa AF: 0.0647 Hom.: 44

Bravo AF: 0.0733

Asia WGS AF: 0.183 AC: 633 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	17
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3740053; hg19: chr10-69644335;