10-67891029-CAAAAAA-CAAAA

Variant names:

• chr10-67891029-CAA-C
• rs11327756
• NM_012238.5:c.790-360_790-359delAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_012238.5(SIRT1):​c.790-360_790-359delAA 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 0.036 (325 hom., cov: 0)
• Consequence: SIRT1 NM_012238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT1	NM_012238.5	c.790-360_790-359delAA		intron_variant	Intron 3 of 8	ENST00000212015.11	NP_036370.2
SIRT1	NM_001142498.2	c.-96-360_-96-359delAA		intron_variant	Intron 2 of 7		NP_001135970.1
SIRT1	NM_001314049.2	c.-245-360_-245-359delAA		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.790-372_790-371delAA		intron_variant	Intron 3 of 8	1	NM_012238.5	ENSP00000212015.6
SIRT1	ENST00000432464.5	c.-96-372_-96-371delAA		intron_variant	Intron 2 of 7	5		ENSP00000409208.1
SIRT1	ENST00000473922.1	n.334-372_334-371delAA		intron_variant	Intron 2 of 3	4
SIRT1	ENST00000497639.5	n.579-372_579-371delAA		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.0364 AC: 3658 AN: 100376 Hom.: 323 Cov.: 0

Gnomad AFR AF: 0.00629

Gnomad AMI AF: 0.0364

Gnomad AMR AF: 0.0866

Gnomad ASJ AF: 0.00668

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.00885

Gnomad NFE AF: 0.00415

Gnomad OTH AF: 0.0306

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

GnomAD4 genome AF: 0.0365 AC: 3661 AN: 100384 Hom.: 325 Cov.: 0 AF XY: 0.0438 AC XY: 2092 AN XY: 47750

Gnomad4 AFR AF: 0.00628

Gnomad4 AMR AF: 0.0874

Gnomad4 ASJ AF: 0.00668

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.0548

Gnomad4 NFE AF: 0.00415

Gnomad4 OTH AF: 0.0304

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs11327756; hg19: chr10-69650787;