rs35689145

chr10-67900009-G-Achr10-67900009-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012238.5(SIRT1):c.943-6781G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0636 in 152,054 control chromosomes in the GnomAD database, including 330 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 0.064 (330 hom., cov: 31)
• Consequence: SIRT1 NM_012238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.616

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRT1	NM_012238.5	c.943-6781G>A		intron_variant		ENST00000212015.11
SIRT1	NM_001142498.2	c.58-6781G>A		intron_variant
SIRT1	NM_001314049.2	c.-92-6154G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRT1	ENST00000212015.11	c.943-6781G>A		intron_variant		1	NM_012238.5	P1
SIRT1	ENST00000406900.5	c.-92-6154G>A		intron_variant		2
SIRT1	ENST00000432464.5	c.58-6781G>A		intron_variant		5
SIRT1	ENST00000473922.1	n.487-6781G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0637 AC: 9681 AN: 151938 Hom.: 329 Cov.: 31

Gnomad AFR AF: 0.0351

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0522

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.0511

Gnomad FIN AF: 0.0567

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0817

Gnomad OTH AF: 0.0657

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

GnomAD4 genome AF: 0.0636 AC: 9678 AN: 152054 Hom.: 330 Cov.: 31 AF XY: 0.0618 AC XY: 4594 AN XY: 74316

Gnomad4 AFR AF: 0.0351

Gnomad4 AMR AF: 0.0521

Gnomad4 ASJ AF: 0.0761

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.0514

Gnomad4 FIN AF: 0.0567

Gnomad4 NFE AF: 0.0817

Gnomad4 OTH AF: 0.0640

Alfa AF: 0.0244 Hom.: 13

Bravo AF: 0.0609

Asia WGS AF: 0.0600 AC: 208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	3.2
Dann	Benign	0.76

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: rs35689145; hg19: chr10-69659767; COSMIC: COSV53020104;