10-67910388-C-G

Variant names:

• chr10-67910388-C-G
• rs17526356
• NM_012238.5:c.1357+946C>G

Variant summary

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

The NM_012238.5(SIRT1):​c.1357+946C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 151,856 control chromosomes in the GnomAD database, including 20,695 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 (20695 hom., cov: 31)
• Consequence: SIRT1 NM_012238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299

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=-0.83).
• 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 rank	MANE	Protein	UniProt
SIRT1	NM_012238.5	c.1357+946C>G		intron_variant	Intron 7 of 8	ENST00000212015.11	NP_036370.2
SIRT1	NM_001142498.2	c.472+946C>G		intron_variant	Intron 6 of 7		NP_001135970.1
SIRT1	NM_001314049.2	c.448+946C>G		intron_variant	Intron 8 of 9		NP_001300978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT1	ENST00000212015.11	c.1357+946C>G		intron_variant	Intron 7 of 8	1	NM_012238.5	ENSP00000212015.6
SIRT1	ENST00000403579.1	c.448+946C>G		intron_variant	Intron 4 of 5	1		ENSP00000384063.1
SIRT1	ENST00000432464.5	c.472+946C>G		intron_variant	Intron 6 of 7	5		ENSP00000409208.1
SIRT1	ENST00000406900.5	c.448+946C>G		intron_variant	Intron 5 of 6	2		ENSP00000384508.1

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71192 AN: 151756 Hom.: 20699 Cov.: 31

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.469 AC: 71180 AN: 151856 Hom.: 20695 Cov.: 31 AF XY: 0.465 AC XY: 34511 AN XY: 74204

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.670

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.510

Alfa AF: 0.547 Hom.: 3093

Bravo AF: 0.444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.49

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: rs17526356; hg19: chr10-69670145;