rs737477

Variant names:

• chr10-67887847-A-C
• rs737477
• NM_012238.5:c.547+314A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-67887847-A-C
• chr10-67887847-A-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.547+314A>C 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 152,274 control chromosomes in the GnomAD database, including 710 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 (710 hom., cov: 33)
• Consequence: SIRT1 NM_012238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• Publications: 4 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=-0.91).
• 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 rank	MANE	Protein	UniProt
SIRT1	NM_012238.5	c.547+314A>C		intron_variant	Intron 2 of 8	ENST00000212015.11	NP_036370.2
SIRT1	NM_001142498.2	c.-97+314A>C		intron_variant	Intron 2 of 7		NP_001135970.1
SIRT1	NM_001314049.2	c.-488+314A>C		intron_variant	Intron 2 of 9		NP_001300978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT1	ENST00000212015.11	c.547+314A>C		intron_variant	Intron 2 of 8	1	NM_012238.5	ENSP00000212015.6
SIRT1	ENST00000432464.5	c.-97+314A>C		intron_variant	Intron 2 of 7	5		ENSP00000409208.1
SIRT1	ENST00000473922.1	n.333+314A>C		intron_variant	Intron 2 of 3	4
SIRT1	ENST00000497639.5	n.336+314A>C		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.0755 AC: 11486 AN: 152152 Hom.: 709 Cov.: 33

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: 0.125

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0653

Gnomad OTH AF: 0.0738

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

GnomAD4 genome AF: 0.0754 AC: 11484 AN: 152274 Hom.: 710 Cov.: 33 AF XY: 0.0811 AC XY: 6034 AN XY: 74438

African (AFR) AF: 0.0265 AC: 1100 AN: 41574

American (AMR) AF: 0.118 AC: 1810 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3466

East Asian (EAS) AF: 0.302 AC: 1562 AN: 5170

South Asian (SAS) AF: 0.123 AC: 596 AN: 4826

European-Finnish (FIN) AF: 0.148 AC: 1567 AN: 10600

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0653 AC: 4440 AN: 68030

Other (OTH) AF: 0.0725 AC: 153 AN: 2110

Alfa AF: 0.0309 Hom.: 24

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	-0.91
CADD	Benign	1.9
DANN	Benign	0.77
PhyloP100		-0.19
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: rs737477; hg19: chr10-69647605;