dbSNP rs3847968: ENSG00000310566:n.172C>T (chr12-120293066-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000850922.1(ENSG00000310566):n.172C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 124,676 control chromosomes in the GnomAD database, including 359 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 0.069 ( 359 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ENSG00000310566
ENST00000850922.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.17

Publications

1 publications found

Variant links:

Genes affected

ENSG00000310566 (HGNC:):

ENSG00000310566 links:

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]

SIRT4 links:

RNU4-1 (HGNC:10192): (RNA, U4 small nuclear 1)

RNU4-1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
SIRT4	XM_006719309.5 link	c.-230G>A	5_prime_UTR_variant	Exon 1 of 4	XP_006719372.1
SIRT4	NM_001385733.2 link	c.-2+124G>A	intron_variant	Intron 1 of 3	NP_001372662.1
SIRT4	NM_001385735.2 link	c.-2+124G>A	intron_variant	Intron 1 of 3	NP_001372664.1
RNU4-1	NR_003925.2 link	n.*27C>T	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
ENSG00000310566	ENST00000850922.1 link	n.172C>T	non_coding_transcript_exon_variant	Exon 1 of 6
ENSG00000310566	ENST00000850923.1 link	n.172C>T	non_coding_transcript_exon_variant	Exon 1 of 3
ENSG00000310566	ENST00000850924.1 link	n.172C>T	non_coding_transcript_exon_variant	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0690

AC:

8600

AN:

124556

Hom.:

358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0394

Gnomad AMI

AF:

0.0591

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.0255

Gnomad EAS

AF:

0.123

Gnomad SAS

AF:

0.0953

Gnomad FIN

AF:

0.0891

Gnomad MID

AF:

0.0362

Gnomad NFE

AF:

0.0595

Gnomad OTH

AF:

0.0690

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0692

AC:

8622

AN:

124676

Hom.:

359

Cov.:

AF XY:

0.0741

AC XY:

4444

AN XY:

59978

show subpopulations

African (AFR)

AF:

0.0398

AC:

1390

AN:

34888

American (AMR)

AF:

0.178

AC:

2152

AN:

12060

Ashkenazi Jewish (ASJ)

AF:

0.0255

AC:

AN:

3134

East Asian (EAS)

AF:

0.124

AC:

413

AN:

3338

South Asian (SAS)

AF:

0.0943

AC:

287

AN:

3042

European-Finnish (FIN)

AF:

0.0891

AC:

700

AN:

7860

Middle Eastern (MID)

AF:

0.0388

AC:

AN:

258

European-Non Finnish (NFE)

AF:

0.0595

AC:

3430

AN:

57652

Other (OTH)

AF:

0.0682

AC:

116

AN:

1700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

405

809

1214

1618

2023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0520

Hom.:

392

Bravo

AF:

0.0622

Asia WGS

AF:

0.0710

AC:

246

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.0020

(source)

DANN

Benign

0.60

PhyloP100

-1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over