10-67913488-C-G

Position:

• chr10-67913488-C-G

Variant summary

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

The NM_012238.5(SIRT1):​c.1915+457C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,052 control chromosomes in the GnomAD database, including 30,667 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 0.63 (30667 hom., cov: 32)
• Consequence: SIRT1 NM_012238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIRT1	NM_012238.5	c.1915+457C>G		intron_variant		ENST00000212015.11	NP_036370.2
SIRT1	NM_001142498.2	c.1030+457C>G		intron_variant			NP_001135970.1
SIRT1	NM_001314049.2	c.1006+457C>G		intron_variant			NP_001300978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIRT1	ENST00000212015.11	c.1915+457C>G		intron_variant		1	NM_012238.5	ENSP00000212015	P1
SIRT1	ENST00000403579.1	c.1006+457C>G		intron_variant		1		ENSP00000384063
SIRT1	ENST00000406900.5	c.1006+457C>G		intron_variant		2		ENSP00000384508
SIRT1	ENST00000432464.5	c.1030+457C>G		intron_variant		5		ENSP00000409208

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95169 AN: 151934 Hom.: 30646 Cov.: 32

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.626 AC: 95230 AN: 152052 Hom.: 30667 Cov.: 32 AF XY: 0.617 AC XY: 45853 AN XY: 74306

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.627

Alfa AF: 0.546 Hom.: 1563

Bravo AF: 0.622

Asia WGS AF: 0.389 AC: 1356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.70

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: rs7091896; hg19: chr10-69673245;