rs7896005

chr10-67891367-A-Gchr10-67891367-A-T

Variant summary

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

The NM_012238.5(SIRT1):c.790-35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 1,602,388 control chromosomes in the GnomAD database, including 295,214 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 0.47 (20724 hom., cov: 32)
  • Exomes 𝑓: 0.60 (274490 hom.)
• Consequence: SIRT1 NM_012238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

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=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRT1	NM_012238.5	c.790-35A>G		intron_variant		ENST00000212015.11
SIRT1	NM_001142498.2	c.-96-35A>G		intron_variant
SIRT1	NM_001314049.2	c.-245-35A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRT1	ENST00000212015.11	c.790-35A>G		intron_variant		1	NM_012238.5	P1
SIRT1	ENST00000432464.5	c.-96-35A>G		intron_variant		5
SIRT1	ENST00000473922.1	n.334-35A>G		intron_variant, non_coding_transcript_variant		4
SIRT1	ENST00000497639.5	n.579-35A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71266 AN: 151978 Hom.: 20728 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.506

GnomAD3 exomes AF: 0.515 AC: 128093 AN: 248520 Hom.: 37366 AF XY: 0.528 AC XY: 70923 AN XY: 134322

Gnomad AFR exome AF: 0.128

Gnomad AMR exome AF: 0.401

Gnomad ASJ exome AF: 0.672

Gnomad EAS exome AF: 0.145

Gnomad SAS exome AF: 0.438

Gnomad FIN exome AF: 0.582

Gnomad NFE exome AF: 0.657

Gnomad OTH exome AF: 0.574

GnomAD4 exome AF: 0.602 AC: 872500 AN: 1450292 Hom.: 274490 Cov.: 26 AF XY: 0.600 AC XY: 432814 AN XY: 721444

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.421

Gnomad4 ASJ exome AF: 0.679

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.589

Gnomad4 NFE exome AF: 0.652

Gnomad4 OTH exome AF: 0.576

GnomAD4 genome AF: 0.468 AC: 71255 AN: 152096 Hom.: 20724 Cov.: 32 AF XY: 0.465 AC XY: 34567 AN XY: 74350

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.510

Alfa AF: 0.566 Hom.: 5521

Bravo AF: 0.444

Asia WGS AF: 0.345 AC: 1202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	14
Dann	Benign	0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7896005; hg19: chr10-69651125; COSMIC: COSV53019771; COSMIC: COSV53019771;