rs2236318

Variant names:

• chr10-67888811-T-A
• rs2236318
• NM_012238.5:c.548-71T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-67888811-T-A
• chr10-67888811-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012238.5(SIRT1):​c.548-71T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,512,402 control chromosomes in the GnomAD database, including 195,200 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 0.38 (14003 hom., cov: 32)
  • Exomes 𝑓: 0.50 (181197 hom.)
• Consequence: SIRT1 NM_012238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 10 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=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT1	NM_012238.5	c.548-71T>A		intron_variant	Intron 2 of 8	ENST00000212015.11	NP_036370.2
SIRT1	NM_001142498.2	c.-97+1278T>A		intron_variant	Intron 2 of 7		NP_001135970.1
SIRT1	NM_001314049.2	c.-487-71T>A		intron_variant	Intron 2 of 9		NP_001300978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT1	ENST00000212015.11	c.548-71T>A		intron_variant	Intron 2 of 8	1	NM_012238.5	ENSP00000212015.6
SIRT1	ENST00000432464.5	c.-97+1278T>A		intron_variant	Intron 2 of 7	5		ENSP00000409208.1
SIRT1	ENST00000473922.1	n.333+1278T>A		intron_variant	Intron 2 of 3	4
SIRT1	ENST00000497639.5	n.337-71T>A		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58159 AN: 151970 Hom.: 14007 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.415

GnomAD4 exome AF: 0.502 AC: 682800 AN: 1360314 Hom.: 181197 AF XY: 0.498 AC XY: 333393 AN XY: 669968

African (AFR) AF: 0.0864 AC: 2620 AN: 30314

American (AMR) AF: 0.381 AC: 11970 AN: 31446

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 12485 AN: 21466

East Asian (EAS) AF: 0.122 AC: 4744 AN: 38832

South Asian (SAS) AF: 0.271 AC: 19141 AN: 70622

European-Finnish (FIN) AF: 0.467 AC: 22227 AN: 47582

Middle Eastern (MID) AF: 0.424 AC: 2272 AN: 5356

European-Non Finnish (NFE) AF: 0.548 AC: 580390 AN: 1058572

Other (OTH) AF: 0.480 AC: 26951 AN: 56124

GnomAD4 genome AF: 0.382 AC: 58144 AN: 152088 Hom.: 14003 Cov.: 32 AF XY: 0.377 AC XY: 27988 AN XY: 74332

African (AFR) AF: 0.104 AC: 4305 AN: 41546

American (AMR) AF: 0.419 AC: 6389 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1990 AN: 3472

East Asian (EAS) AF: 0.124 AC: 642 AN: 5178

South Asian (SAS) AF: 0.278 AC: 1340 AN: 4818

European-Finnish (FIN) AF: 0.464 AC: 4895 AN: 10552

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37219 AN: 67944

Other (OTH) AF: 0.418 AC: 883 AN: 2112

Alfa AF: 0.443 Hom.: 2095

Bravo AF: 0.367

Asia WGS AF: 0.226 AC: 791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		1.3
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: rs2236318; hg19: chr10-69648569; COSMIC: COSV53018370; COSMIC: COSV53018370;