rs10997870

Variant names:

• chr10-67908257-G-T
• rs10997870
• NM_012238.5:c.1170+132G>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.1170+132G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 685,878 control chromosomes in the GnomAD database, including 119,825 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 (20723 hom., cov: 32)
  • Exomes 𝑓: 0.59 (99102 hom.)
• Consequence: SIRT1 NM_012238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 26 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 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.1170+132G>T		intron	N/A	NP_036370.2
	SIRT1	NM_001142498.2		c.285+132G>T		intron	N/A	NP_001135970.1	E9PC49
	SIRT1	NM_001314049.2		c.261+132G>T		intron	N/A	NP_001300978.1	B0QZ35

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT1	ENST00000212015.11	TSL:1 MANE Select	c.1170+132G>T		intron	N/A	ENSP00000212015.6	Q96EB6-1
	SIRT1	ENST00000403579.1	TSL:1	c.261+132G>T		intron	N/A	ENSP00000384063.1	B0QZ35
	SIRT1	ENST00000923649.1		c.1389+132G>T		intron	N/A	ENSP00000593708.1

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71269 AN: 151888 Hom.: 20727 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.505

GnomAD4 exome AF: 0.591 AC: 315338 AN: 533872 Hom.: 99102 AF XY: 0.588 AC XY: 162089 AN XY: 275736

African (AFR) AF: 0.137 AC: 1781 AN: 13044

American (AMR) AF: 0.469 AC: 6755 AN: 14406

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 9010 AN: 13224

East Asian (EAS) AF: 0.165 AC: 4879 AN: 29534

South Asian (SAS) AF: 0.433 AC: 15359 AN: 35450

European-Finnish (FIN) AF: 0.590 AC: 21247 AN: 35996

Middle Eastern (MID) AF: 0.562 AC: 1180 AN: 2100

European-Non Finnish (NFE) AF: 0.660 AC: 239366 AN: 362692

Other (OTH) AF: 0.575 AC: 15761 AN: 27426

GnomAD4 genome AF: 0.469 AC: 71258 AN: 152006 Hom.: 20723 Cov.: 32 AF XY: 0.465 AC XY: 34560 AN XY: 74258

African (AFR) AF: 0.138 AC: 5738 AN: 41486

American (AMR) AF: 0.503 AC: 7680 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2326 AN: 3470

East Asian (EAS) AF: 0.150 AC: 779 AN: 5178

South Asian (SAS) AF: 0.441 AC: 2126 AN: 4820

European-Finnish (FIN) AF: 0.587 AC: 6170 AN: 10518

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.658 AC: 44744 AN: 67964

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

Alfa AF: 0.611 Hom.: 34085

Bravo AF: 0.444

Asia WGS AF: 0.346 AC: 1203 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.3
DANN	Benign	0.41
PhyloP100		1.2
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: rs10997870; hg19: chr10-69668014; COSMIC: COSV53017552; COSMIC: COSV53017552;