rs3818292

chr10-67907144-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012238.5(SIRT1):c.1090+207A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0754 in 152,284 control chromosomes in the GnomAD database, including 708 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 0.075 (708 hom., cov: 32)
• Consequence: SIRT1 NM_012238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRT1	NM_012238.5	c.1090+207A>G		intron_variant		ENST00000212015.11
SIRT1	NM_001142498.2	c.205+207A>G		intron_variant
SIRT1	NM_001314049.2	c.181+207A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRT1	ENST00000212015.11	c.1090+207A>G		intron_variant		1	NM_012238.5	P1
SIRT1	ENST00000403579.1	c.181+207A>G		intron_variant		1
SIRT1	ENST00000406900.5	c.181+207A>G		intron_variant		2
SIRT1	ENST00000432464.5	c.205+207A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0754 AC: 11480 AN: 152166 Hom.: 707 Cov.: 32

Gnomad AFR AF: 0.0265

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0652

Gnomad OTH AF: 0.0733

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

GnomAD4 genome AF: 0.0754 AC: 11478 AN: 152284 Hom.: 708 Cov.: 32 AF XY: 0.0810 AC XY: 6031 AN XY: 74452

Gnomad4 AFR AF: 0.0265

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0444

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.0652

Gnomad4 OTH AF: 0.0720

Alfa AF: 0.0688 Hom.: 62

Bravo AF: 0.0727

Asia WGS AF: 0.182 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.43
Dann	Benign	0.43

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: rs3818292; hg19: chr10-69666901;