10-67884459-A-C

Variant names:

• chr10-67884459-A-C
• rs932658
• NM_012238.5:c.-263A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012238.5(SIRT1):​c.-263A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,154 control chromosomes in the GnomAD database, including 30,717 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 0.63 (30717 hom., cov: 34)
• Consequence: SIRT1 NM_012238.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300
• Publications: 25 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=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT1	NM_012238.5	c.-263A>C		upstream_gene_variant		ENST00000212015.11	NP_036370.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT1	ENST00000212015.11	c.-263A>C		upstream_gene_variant		1	NM_012238.5	ENSP00000212015.6

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95264 AN: 152036 Hom.: 30698 Cov.: 34

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.626 AC: 95323 AN: 152154 Hom.: 30717 Cov.: 34 AF XY: 0.617 AC XY: 45924 AN XY: 74374

African (AFR) AF: 0.648 AC: 26893 AN: 41514

American (AMR) AF: 0.569 AC: 8706 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2374 AN: 3470

East Asian (EAS) AF: 0.152 AC: 783 AN: 5158

South Asian (SAS) AF: 0.456 AC: 2200 AN: 4826

European-Finnish (FIN) AF: 0.591 AC: 6267 AN: 10600

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.678 AC: 46112 AN: 67980

Other (OTH) AF: 0.626 AC: 1323 AN: 2112

Alfa AF: 0.557 Hom.: 1740

Bravo AF: 0.622

Asia WGS AF: 0.388 AC: 1352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.1
DANN	Benign	0.51
PhyloP100		0.0030
PromoterAI		-0.10	Neutral

Splicing

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

Other links and lift over

dbSNP: rs932658; hg19: chr10-69644217;