dbSNP rs4746720: SIRT1:c.*480T>C (chr10-67917073-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012238.5(SIRT1):c.*480T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 152,736 control chromosomes in the GnomAD database, including 532 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 0.030 ( 532 hom., cov: 32)

Exomes 𝑓: 0.043 ( 0 hom. )

Consequence

SIRT1
NM_012238.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.64

Publications

58 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SIRT1	NM_012238.5 link	c.*480T>C	3_prime_UTR_variant	Exon 9 of 9	ENST00000212015.11	NP_036370.2	Q96EB6-1A0A024QZQ1
SIRT1	NM_001142498.2 link	c.*480T>C	3_prime_UTR_variant	Exon 8 of 8		NP_001135970.1	Q96EB6A8K128E9PC49
SIRT1	NM_001314049.2 link	c.*480T>C	3_prime_UTR_variant	Exon 10 of 10		NP_001300978.1	Q96EB6B0QZ35

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SIRT1	ENST00000212015.11 link	c.*480T>C	3_prime_UTR_variant	Exon 9 of 9	1	NM_012238.5	ENSP00000212015.6	Q96EB6-1
SIRT1	ENST00000403579.1 link	c.*480T>C	3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000384063.1	B0QZ35
SIRT1	ENST00000432464.5 link	c.*480T>C	3_prime_UTR_variant	Exon 8 of 8	5		ENSP00000409208.1	E9PC49
SIRT1	ENST00000406900.5 link	c.*480T>C	3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000384508.1	B0QZ35

Frequencies

GnomAD3 genomes

AF:

0.0302

AC:

4594

AN:

152158

Hom.:

529

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00478

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0689

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.415

Gnomad SAS

AF:

0.0973

Gnomad FIN

AF:

0.0404

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00295

Gnomad OTH

AF:

0.0244

GnomAD4 exome

AF:

0.0435

AC:

AN:

460

Hom.:

Cov.:

AF XY:

0.0331

AC XY:

AN XY:

272

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0444

AC:

AN:

428

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0500

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0302

AC:

4602

AN:

152276

Hom.:

532

Cov.:

AF XY:

0.0367

AC XY:

2733

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.00476

AC:

198

AN:

41566

American (AMR)

AF:

0.0697

AC:

1066

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3468

East Asian (EAS)

AF:

0.414

AC:

2142

AN:

5170

South Asian (SAS)

AF:

0.0974

AC:

470

AN:

4826

European-Finnish (FIN)

AF:

0.0404

AC:

429

AN:

10610

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00295

AC:

201

AN:

68026

Other (OTH)

AF:

0.0246

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

177

354

532

709

886

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0148

Hom.:

489

Bravo

AF:

0.0347

Asia WGS

AF:

0.211

AC:

732

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.5

(source)

DANN

Benign

0.80

PhyloP100

1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over