rs3818292

Variant names:

• chr10-67907144-A-G
• rs3818292
• NM_012238.5:c.1090+207A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 33 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.29 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT1	NM_012238.5	MANE Select	c.1090+207A>G		intron	N/A	NP_036370.2
	SIRT1	NM_001142498.2		c.205+207A>G		intron	N/A	NP_001135970.1
	SIRT1	NM_001314049.2		c.181+207A>G		intron	N/A	NP_001300978.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT1	ENST00000212015.11	TSL:1 MANE Select	c.1090+207A>G		intron	N/A	ENSP00000212015.6
	SIRT1	ENST00000403579.1	TSL:1	c.181+207A>G		intron	N/A	ENSP00000384063.1
	SIRT1	ENST00000432464.5	TSL:5	c.205+207A>G		intron	N/A	ENSP00000409208.1

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

African (AFR) AF: 0.0265 AC: 1101 AN: 41588

American (AMR) AF: 0.118 AC: 1813 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3472

East Asian (EAS) AF: 0.303 AC: 1567 AN: 5178

South Asian (SAS) AF: 0.124 AC: 596 AN: 4824

European-Finnish (FIN) AF: 0.147 AC: 1555 AN: 10580

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0652 AC: 4438 AN: 68020

Other (OTH) AF: 0.0720 AC: 152 AN: 2110

Alfa AF: 0.0676 Hom.: 62

Bravo AF: 0.0727

Asia WGS AF: 0.182 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.43
DANN	Benign	0.43
PhyloP100		-0.29
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: rs3818292; hg19: chr10-69666901;