rs12413112

Variant names:

• chr10-67892108-G-A
• rs12413112
• NM_012238.5:c.942+554G>A

Variant summary

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

The NM_012238.5(SIRT1):​c.942+554G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,152 control chromosomes in the GnomAD database, including 964 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 0.11 (964 hom., cov: 32)
• Consequence: SIRT1 NM_012238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479
• Publications: 22 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT1	NM_012238.5	c.942+554G>A		intron_variant	Intron 4 of 8	ENST00000212015.11	NP_036370.2
SIRT1	NM_001142498.2	c.57+554G>A		intron_variant	Intron 3 of 7		NP_001135970.1
SIRT1	NM_001314049.2	c.-93+554G>A		intron_variant	Intron 4 of 9		NP_001300978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT1	ENST00000212015.11	c.942+554G>A		intron_variant	Intron 4 of 8	1	NM_012238.5	ENSP00000212015.6
SIRT1	ENST00000432464.5	c.57+554G>A		intron_variant	Intron 3 of 7	5		ENSP00000409208.1
SIRT1	ENST00000406900.5	c.-93+554G>A		intron_variant	Intron 1 of 6	2		ENSP00000384508.1
SIRT1	ENST00000473922.1	n.486+554G>A		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16875 AN: 152034 Hom.: 964 Cov.: 32

Gnomad AFR AF: 0.0738

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.111 AC: 16891 AN: 152152 Hom.: 964 Cov.: 32 AF XY: 0.111 AC XY: 8274 AN XY: 74384

African (AFR) AF: 0.0738 AC: 3064 AN: 41526

American (AMR) AF: 0.140 AC: 2130 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 467 AN: 3470

East Asian (EAS) AF: 0.130 AC: 672 AN: 5170

South Asian (SAS) AF: 0.146 AC: 706 AN: 4826

European-Finnish (FIN) AF: 0.102 AC: 1076 AN: 10576

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8453 AN: 67998

Other (OTH) AF: 0.116 AC: 246 AN: 2116

Alfa AF: 0.118 Hom.: 136

Bravo AF: 0.110

Asia WGS AF: 0.127 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.36
DANN	Benign	0.44
PhyloP100		-0.48
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: rs12413112; hg19: chr10-69651866;