rs3818292

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.289
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SIRT1NM_012238.5 linkuse as main transcriptc.1090+207A>G intron_variant ENST00000212015.11
SIRT1NM_001142498.2 linkuse as main transcriptc.205+207A>G intron_variant
SIRT1NM_001314049.2 linkuse as main transcriptc.181+207A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SIRT1ENST00000212015.11 linkuse as main transcriptc.1090+207A>G intron_variant 1 NM_012238.5 P1Q96EB6-1
SIRT1ENST00000403579.1 linkuse as main transcriptc.181+207A>G intron_variant 1
SIRT1ENST00000406900.5 linkuse as main transcriptc.181+207A>G intron_variant 2
SIRT1ENST00000432464.5 linkuse as main transcriptc.205+207A>G intron_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0754
AC:
11480
AN:
152166
Hom.:
707
Cov.:
32
show subpopulations
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
show subpopulations
Gnomad4 AFR
AF:
0.0265
Gnomad4 AMR
AF:
0.118
Gnomad4 ASJ
AF:
0.0444
Gnomad4 EAS
AF:
0.303
Gnomad4 SAS
AF:
0.124
Gnomad4 FIN
AF:
0.147
Gnomad4 NFE
AF:
0.0652
Gnomad4 OTH
AF:
0.0720
Alfa
AF:
0.0688
Hom.:
62
Bravo
AF:
0.0727
Asia WGS
AF:
0.182
AC:
631
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.43
DANN
Benign
0.43

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3818292; hg19: chr10-69666901; API