rs7896005

Variant names:

• chr10-67891367-A-G
• rs7896005
• NM_012238.5:c.790-35A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-67891367-A-G
• chr10-67891367-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 46 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=-0.58).
• 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 rank	MANE	Protein	UniProt
SIRT1	NM_012238.5	c.790-35A>G		intron_variant	Intron 3 of 8	ENST00000212015.11	NP_036370.2
SIRT1	NM_001142498.2	c.-96-35A>G		intron_variant	Intron 2 of 7		NP_001135970.1
SIRT1	NM_001314049.2	c.-245-35A>G		intron_variant	Intron 3 of 9		NP_001300978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT1	ENST00000212015.11	c.790-35A>G		intron_variant	Intron 3 of 8	1	NM_012238.5	ENSP00000212015.6

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

GnomAD2 exomes AF: 0.515 AC: 128093 AN: 248520 AF XY: 0.528

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 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

African (AFR) AF: 0.124 AC: 4101 AN: 33142

American (AMR) AF: 0.421 AC: 18542 AN: 44082

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 17604 AN: 25932

East Asian (EAS) AF: 0.162 AC: 6419 AN: 39560

South Asian (SAS) AF: 0.438 AC: 37375 AN: 85334

European-Finnish (FIN) AF: 0.589 AC: 31363 AN: 53272

Middle Eastern (MID) AF: 0.534 AC: 3056 AN: 5726

European-Non Finnish (NFE) AF: 0.652 AC: 719537 AN: 1103312

Other (OTH) AF: 0.576 AC: 34503 AN: 59932

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

African (AFR) AF: 0.138 AC: 5726 AN: 41510

American (AMR) AF: 0.504 AC: 7687 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2328 AN: 3472

East Asian (EAS) AF: 0.149 AC: 773 AN: 5176

South Asian (SAS) AF: 0.440 AC: 2118 AN: 4812

European-Finnish (FIN) AF: 0.584 AC: 6175 AN: 10568

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44749 AN: 67974

Other (OTH) AF: 0.510 AC: 1079 AN: 2116

Alfa AF: 0.556 Hom.: 5530

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
PhyloP100		1.4
PromoterAI		0.0086	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7896005; hg19: chr10-69651125; COSMIC: COSV53019771; COSMIC: COSV53019771;