rs2236319

Positions:

• chr10-67889462-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.789+339A>G 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 152,216 control chromosomes in the GnomAD database, including 713 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 (713 hom., cov: 32)
• Consequence: SIRT1 NM_012238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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=-0.9).
• 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	Protein	UniProt
SIRT1	NM_012238.5	c.789+339A>G		intron_variant		ENST00000212015.11	NP_036370.2
SIRT1	NM_001142498.2	c.-97+1929A>G		intron_variant			NP_001135970.1
SIRT1	NM_001314049.2	c.-246+339A>G		intron_variant			NP_001300978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIRT1	ENST00000212015.11	c.789+339A>G		intron_variant		1	NM_012238.5	ENSP00000212015	P1
SIRT1	ENST00000432464.5	c.-97+1929A>G		intron_variant		5		ENSP00000409208
SIRT1	ENST00000473922.1	n.333+1929A>G		intron_variant, non_coding_transcript_variant		4
SIRT1	ENST00000497639.5	n.578+339A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0755 AC: 11482 AN: 152096 Hom.: 712 Cov.: 32

Gnomad AFR AF: 0.0265

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0653

Gnomad OTH AF: 0.0732

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

GnomAD4 genome AF: 0.0754 AC: 11480 AN: 152216 Hom.: 713 Cov.: 32 AF XY: 0.0810 AC XY: 6031 AN XY: 74412

Gnomad4 AFR AF: 0.0264

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.0441

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.0653

Gnomad4 OTH AF: 0.0720

Alfa AF: 0.0681 Hom.: 209

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	-0.90
CADD	Benign	0.17
DANN	Benign	0.44

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: rs2236319; hg19: chr10-69649220;