rs10997870

Positions:

• chr10-67908257-G-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRT1	NM_012238.5	c.1170+132G>T		intron_variant		ENST00000212015.11
SIRT1	NM_001142498.2	c.285+132G>T		intron_variant
SIRT1	NM_001314049.2	c.261+132G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRT1	ENST00000212015.11	c.1170+132G>T		intron_variant		1	NM_012238.5	P1
SIRT1	ENST00000403579.1	c.261+132G>T		intron_variant		1
SIRT1	ENST00000406900.5	c.261+132G>T		intron_variant		2
SIRT1	ENST00000432464.5	c.285+132G>T		intron_variant		5

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

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.469

Gnomad4 ASJ exome AF: 0.681

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.433

Gnomad4 FIN exome AF: 0.590

Gnomad4 NFE exome AF: 0.660

Gnomad4 OTH exome AF: 0.575

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

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.670

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.509

Alfa AF: 0.619 Hom.: 28692

Bravo AF: 0.444

Asia WGS AF: 0.346 AC: 1203 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.3
DANN	Benign	0.41

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: rs10997870; hg19: chr10-69668014; COSMIC: COSV53017552; COSMIC: COSV53017552;