10-67891029-CAAAAAA-CAAAAA

Variant names:

• chr10-67891029-CA-C
• rs11327756
• NM_012238.5:c.790-359delA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_012238.5(SIRT1):​c.790-359delA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (5427 hom., cov: 0)
• Consequence: SIRT1 NM_012238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• Publications: 1 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT1	NM_012238.5	c.790-359delA		intron_variant	Intron 3 of 8	ENST00000212015.11	NP_036370.2
SIRT1	NM_001142498.2	c.-96-359delA		intron_variant	Intron 2 of 7		NP_001135970.1
SIRT1	NM_001314049.2	c.-245-359delA		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.790-372delA		intron_variant	Intron 3 of 8	1	NM_012238.5	ENSP00000212015.6
SIRT1	ENST00000432464.5	c.-96-372delA		intron_variant	Intron 2 of 7	5		ENSP00000409208.1
SIRT1	ENST00000473922.1	n.334-372delA		intron_variant	Intron 2 of 3	4
SIRT1	ENST00000497639.5	n.579-372delA		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.430 AC: 42970 AN: 99930 Hom.: 5411 Cov.: 0

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.451

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.430 AC: 42989 AN: 99938 Hom.: 5427 Cov.: 0 AF XY: 0.430 AC XY: 20440 AN XY: 47528

African (AFR) AF: 0.503 AC: 14104 AN: 28032

American (AMR) AF: 0.418 AC: 4132 AN: 9876

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 913 AN: 2376

East Asian (EAS) AF: 0.395 AC: 1634 AN: 4132

South Asian (SAS) AF: 0.456 AC: 1572 AN: 3444

European-Finnish (FIN) AF: 0.423 AC: 1957 AN: 4624

Middle Eastern (MID) AF: 0.461 AC: 94 AN: 204

European-Non Finnish (NFE) AF: 0.391 AC: 17717 AN: 45272

Other (OTH) AF: 0.435 AC: 585 AN: 1346

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11327756; hg19: chr10-69650787;