Variant rs7896005 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_012238.5(SIRT1):c.790-35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 1,602,388 control chromosomes in the GnomAD database, including 295,214 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 ( 20724 hom., cov: 32)

Exomes 𝑓: 0.60 ( 274490 hom. )

Consequence

SIRT1
NM_012238.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.42

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]

SIRT1 links:

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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=-0.58).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
SIRT1	NM_012238.5 linkuse as main transcript	c.790-35A>G	intron_variant	ENST00000212015.11	NP_036370.2
SIRT1	NM_001142498.2 linkuse as main transcript	c.-96-35A>G	intron_variant		NP_001135970.1
SIRT1	NM_001314049.2 linkuse as main transcript	c.-245-35A>G	intron_variant		NP_001300978.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
SIRT1	ENST00000212015.11 linkuse as main transcript	c.790-35A>G	intron_variant	1	NM_012238.5	ENSP00000212015	P1	Q96EB6-1
SIRT1	ENST00000432464.5 linkuse as main transcript	c.-96-35A>G	intron_variant	5		ENSP00000409208
SIRT1	ENST00000473922.1 linkuse as main transcript	n.334-35A>G	intron_variant, non_coding_transcript_variant	4
SIRT1	ENST00000497639.5 linkuse as main transcript	n.579-35A>G	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

71266

AN:

151978

Hom.:

20728

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.492

Gnomad AMR

AF:

0.505

Gnomad ASJ

AF:

0.671

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.440

Gnomad FIN

AF:

0.584

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.658

Gnomad OTH

AF:

0.506

GnomAD3 exomes

AF:

0.515

AC:

128093

AN:

248520

Hom.:

37366

AF XY:

0.528

AC XY:

70923

AN XY:

134322

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.401

Gnomad ASJ exome

AF:

0.672

Gnomad EAS exome

AF:

0.145

Gnomad SAS exome

AF:

0.438

Gnomad FIN exome

AF:

0.582

Gnomad NFE exome

AF:

0.657

Gnomad OTH exome

AF:

0.574

GnomAD4 exome

AF:

0.602

AC:

872500

AN:

1450292

Hom.:

274490

Cov.:

AF XY:

0.600

AC XY:

432814

AN XY:

721444

show subpopulations

Gnomad4 AFR exome

AF:

0.124

Gnomad4 AMR exome

AF:

0.421

Gnomad4 ASJ exome

AF:

0.679

Gnomad4 EAS exome

AF:

0.162

Gnomad4 SAS exome

AF:

0.438

Gnomad4 FIN exome

AF:

0.589

Gnomad4 NFE exome

AF:

0.652

Gnomad4 OTH exome

AF:

0.576

GnomAD4 genome

AF:

0.468

AC:

71255

AN:

152096

Hom.:

20724

Cov.:

AF XY:

0.465

AC XY:

34567

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.138

Gnomad4 AMR

AF:

0.504

Gnomad4 ASJ

AF:

0.671

Gnomad4 EAS

AF:

0.149

Gnomad4 SAS

AF:

0.440

Gnomad4 FIN

AF:

0.584

Gnomad4 NFE

AF:

0.658

Gnomad4 OTH

AF:

0.510

Alfa

AF:

0.566

Hom.:

5521

Bravo

AF:

0.444

Asia WGS

AF:

0.345

AC:

1202

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over