rs2234975

Variant names:

• chr10-67918321-C-T
• rs2234975
• NM_012238.5:c.*1728C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The NM_012238.5(SIRT1):​c.*1728C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0584 in 152,590 control chromosomes in the GnomAD database, including 342 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 0.058 (341 hom., cov: 33)
  • Exomes 𝑓: 0.074 (1 hom.)
• Consequence: SIRT1 NM_012238.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.85
• Publications: 17 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.15).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT1	NM_012238.5	c.*1728C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000212015.11	NP_036370.2
SIRT1	NM_001142498.2	c.*1728C>T		3_prime_UTR_variant	Exon 8 of 8		NP_001135970.1
SIRT1	NM_001314049.2	c.*1728C>T		3_prime_UTR_variant	Exon 10 of 10		NP_001300978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT1	ENST00000212015.11	c.*1728C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_012238.5	ENSP00000212015.6
SIRT1	ENST00000403579.1	c.*1728C>T		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000384063.1
SIRT1	ENST00000432464.5	c.*1728C>T		3_prime_UTR_variant	Exon 8 of 8	5		ENSP00000409208.1
SIRT1	ENST00000406900.5	c.*1728C>T		3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000384508.1

Frequencies

GnomAD3 genomes AF: 0.0584 AC: 8873 AN: 152040 Hom.: 340 Cov.: 33

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0667

Gnomad ASJ AF: 0.0948

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0190

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0857

Gnomad OTH AF: 0.0736

GnomAD4 exome AF: 0.0741 AC: 32 AN: 432 Hom.: 1 Cov.: 0 AF XY: 0.0923 AC XY: 24 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0751 AC: 32 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0583 AC: 8872 AN: 152158 Hom.: 341 Cov.: 33 AF XY: 0.0556 AC XY: 4139 AN XY: 74380

African (AFR) AF: 0.0160 AC: 663 AN: 41532

American (AMR) AF: 0.0666 AC: 1018 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0948 AC: 329 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0189 AC: 91 AN: 4826

European-Finnish (FIN) AF: 0.0694 AC: 733 AN: 10560

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0857 AC: 5827 AN: 67988

Other (OTH) AF: 0.0728 AC: 154 AN: 2114

Alfa AF: 0.0729 Hom.: 260

Bravo AF: 0.0571

Asia WGS AF: 0.00982 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
CADD	Benign	19
DANN	Benign	0.89
PhyloP100		3.9
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: rs2234975; hg19: chr10-69678078;