NM_012238.5:c.1916-864A>G

Variant names:

• chr10-67915401-A-G
• rs1467568
• NM_012238.5:c.1916-864A>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.1916-864A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 152,148 control chromosomes in the GnomAD database, including 20,629 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 0.46 (20629 hom., cov: 32)
• Consequence: SIRT1 NM_012238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466
• Publications: 45 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT1	NM_012238.5	c.1916-864A>G		intron_variant	Intron 8 of 8	ENST00000212015.11	NP_036370.2
SIRT1	NM_001142498.2	c.1031-864A>G		intron_variant	Intron 7 of 7		NP_001135970.1
SIRT1	NM_001314049.2	c.1007-864A>G		intron_variant	Intron 9 of 9		NP_001300978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT1	ENST00000212015.11	c.1916-864A>G		intron_variant	Intron 8 of 8	1	NM_012238.5	ENSP00000212015.6
SIRT1	ENST00000403579.1	c.1007-864A>G		intron_variant	Intron 5 of 5	1		ENSP00000384063.1
SIRT1	ENST00000432464.5	c.1031-864A>G		intron_variant	Intron 7 of 7	5		ENSP00000409208.1
SIRT1	ENST00000406900.5	c.1007-864A>G		intron_variant	Intron 6 of 6	2		ENSP00000384508.1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70569 AN: 152028 Hom.: 20634 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.464 AC: 70556 AN: 152148 Hom.: 20629 Cov.: 32 AF XY: 0.460 AC XY: 34251 AN XY: 74394

African (AFR) AF: 0.121 AC: 5018 AN: 41530

American (AMR) AF: 0.501 AC: 7663 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2324 AN: 3466

East Asian (EAS) AF: 0.150 AC: 778 AN: 5172

South Asian (SAS) AF: 0.441 AC: 2129 AN: 4826

European-Finnish (FIN) AF: 0.584 AC: 6179 AN: 10584

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44773 AN: 67972

Other (OTH) AF: 0.508 AC: 1070 AN: 2108

Alfa AF: 0.563 Hom.: 4628

Bravo AF: 0.438

Asia WGS AF: 0.343 AC: 1196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.68
PhyloP100		-0.47
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: rs1467568; hg19: chr10-69675158;