rs7137625

Positions:

• chr12-120308574-C-T

Variant summary

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

The ENST00000202967.4(SIRT4):​c.498-3882C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0803 in 152,082 control chromosomes in the GnomAD database, including 1,416 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 0.080 (1416 hom., cov: 31)
• Consequence: SIRT4 ENST00000202967.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441

Genes affected

SIRT4 (HGNC:14932): (sirtuin 4) 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 IV of the sirtuin family. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIRT4	NM_012240.3	c.498-3882C>T		intron_variant		ENST00000202967.4	NP_036372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIRT4	ENST00000202967.4	c.498-3882C>T		intron_variant		1	NM_012240.3	ENSP00000202967	P1
SIRT4	ENST00000537892.1	n.180-4010C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0802 AC: 12186 AN: 151964 Hom.: 1416 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0276

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.0590

Gnomad SAS AF: 0.0319

Gnomad FIN AF: 0.0178

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00254

Gnomad OTH AF: 0.0527

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

GnomAD4 genome AF: 0.0803 AC: 12208 AN: 152082 Hom.: 1416 Cov.: 31 AF XY: 0.0781 AC XY: 5809 AN XY: 74376

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.0276

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.0588

Gnomad4 SAS AF: 0.0324

Gnomad4 FIN AF: 0.0178

Gnomad4 NFE AF: 0.00254

Gnomad4 OTH AF: 0.0521

Alfa AF: 0.0190 Hom.: 269

Bravo AF: 0.0895

Asia WGS AF: 0.0670 AC: 235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.38

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: rs7137625; hg19: chr12-120746377;