rs33957861

Variant names:

• chr10-67887218-C-T
• rs33957861
• NM_012238.5:c.431-199C>T

Variant summary

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

The NM_012238.5(SIRT1):​c.431-199C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,152 control chromosomes in the GnomAD database, including 972 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 0.11 (972 hom., cov: 32)
• Consequence: SIRT1 NM_012238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.887
• Publications: 12 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT1	NM_012238.5	c.431-199C>T		intron_variant	Intron 1 of 8	ENST00000212015.11	NP_036370.2
SIRT1	NM_001142498.2	c.-213-199C>T		intron_variant	Intron 1 of 7		NP_001135970.1
SIRT1	NM_001314049.2	c.-604-199C>T		intron_variant	Intron 1 of 9		NP_001300978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT1	ENST00000212015.11	c.431-199C>T		intron_variant	Intron 1 of 8	1	NM_012238.5	ENSP00000212015.6
SIRT1	ENST00000432464.5	c.-213-199C>T		intron_variant	Intron 1 of 7	5		ENSP00000409208.1
SIRT1	ENST00000473922.1	n.217-199C>T		intron_variant	Intron 1 of 3	4
SIRT1	ENST00000497639.5	n.220-199C>T		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16885 AN: 152034 Hom.: 972 Cov.: 32

Gnomad AFR AF: 0.0739

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.117

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.111 AC: 16901 AN: 152152 Hom.: 972 Cov.: 32 AF XY: 0.111 AC XY: 8272 AN XY: 74380

African (AFR) AF: 0.0739 AC: 3070 AN: 41530

American (AMR) AF: 0.140 AC: 2137 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 467 AN: 3470

East Asian (EAS) AF: 0.130 AC: 674 AN: 5176

South Asian (SAS) AF: 0.147 AC: 707 AN: 4820

European-Finnish (FIN) AF: 0.101 AC: 1069 AN: 10580

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8454 AN: 67976

Other (OTH) AF: 0.116 AC: 246 AN: 2114

Alfa AF: 0.118 Hom.: 136

Bravo AF: 0.110

Asia WGS AF: 0.127 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.9
DANN	Benign	0.88
PhyloP100		0.89
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: rs33957861; hg19: chr10-69646976;