rs737477

chr10-67887847-A-Cchr10-67887847-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SIRT1	NM_012238.5	c.547+314A>C		intron_variant		ENST00000212015.11
SIRT1	NM_001142498.2	c.-97+314A>C		intron_variant
SIRT1	NM_001314049.2	c.-488+314A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRT1	ENST00000212015.11	c.547+314A>C		intron_variant		1	NM_012238.5	P1
SIRT1	ENST00000432464.5	c.-97+314A>C		intron_variant		5
SIRT1	ENST00000473922.1	n.333+314A>C		intron_variant, non_coding_transcript_variant		4
SIRT1	ENST00000497639.5	n.336+314A>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0265

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0444

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.0653

Gnomad4 OTH AF: 0.0725

Alfa AF: 0.0305 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

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

Other links and lift over

dbSNP: rs737477; hg19: chr10-69647605;