rs2394443

Variant names:

• chr10-67884583-G-C
• rs2394443
• NM_012238.5:c.-139G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-67884583-G-C
• chr10-67884583-G-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.-139G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 1,031,224 control chromosomes in the GnomAD database, including 196,586 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 0.47 (20786 hom., cov: 34)
  • Exomes 𝑓: 0.62 (175800 hom.)
• Consequence: SIRT1 NM_012238.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 16 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]

SIRT1 Gene-Disease associations (from GenCC):

• autoimmune disease

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia
• monogenic diabetes

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012238.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT1	NM_012238.5	MANE Select	c.-139G>C		upstream_gene	N/A	NP_036370.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT1	ENST00000212015.11	TSL:1 MANE Select	c.-139G>C		upstream_gene	N/A	ENSP00000212015.6	Q96EB6-1
	SIRT1	ENST00000923649.1		c.-139G>C		upstream_gene	N/A	ENSP00000593708.1
	SIRT1	ENST00000959939.1		c.-139G>C		upstream_gene	N/A	ENSP00000629998.1

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71374 AN: 151954 Hom.: 20790 Cov.: 34

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.593

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.505

GnomAD4 exome AF: 0.622 AC: 546511 AN: 879152 Hom.: 175800 AF XY: 0.623 AC XY: 261571 AN XY: 419626

African (AFR) AF: 0.120 AC: 2197 AN: 18278

American (AMR) AF: 0.491 AC: 3710 AN: 7562

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 8500 AN: 12450

East Asian (EAS) AF: 0.171 AC: 4214 AN: 24614

South Asian (SAS) AF: 0.442 AC: 6569 AN: 14850

European-Finnish (FIN) AF: 0.593 AC: 12127 AN: 20456

Middle Eastern (MID) AF: 0.552 AC: 1383 AN: 2506

European-Non Finnish (NFE) AF: 0.656 AC: 486863 AN: 742220

Other (OTH) AF: 0.578 AC: 20948 AN: 36216

GnomAD4 genome AF: 0.469 AC: 71363 AN: 152072 Hom.: 20786 Cov.: 34 AF XY: 0.466 AC XY: 34629 AN XY: 74338

African (AFR) AF: 0.138 AC: 5726 AN: 41486

American (AMR) AF: 0.504 AC: 7706 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2341 AN: 3470

East Asian (EAS) AF: 0.150 AC: 772 AN: 5144

South Asian (SAS) AF: 0.442 AC: 2133 AN: 4822

European-Finnish (FIN) AF: 0.585 AC: 6198 AN: 10592

Middle Eastern (MID) AF: 0.583 AC: 169 AN: 290

European-Non Finnish (NFE) AF: 0.659 AC: 44793 AN: 67958

Other (OTH) AF: 0.509 AC: 1076 AN: 2112

Alfa AF: 0.553 Hom.: 3248

Bravo AF: 0.444

Asia WGS AF: 0.347 AC: 1208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	9.9
DANN	Benign	0.71
PhyloP100		1.1
PromoterAI		-0.048	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs2394443; hg19: chr10-69644341;