chr16-53779455-T-G

Variant names:

Variant summary

Our verdict is The variant received -14 classification points (ACMG Germline Pathogenicity v2019): 0P and 14B. BA1BP4_StrongBP6_Moderate

The NM_001080432.3(FTO):c.46-30685T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.384 (AC=58,367) in the gnomAD database across 152,026 control chromosomes, including 11,497 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.404. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★).

Frequency

Genomes: 𝑓 0.38 ( 11497 hom., cov: 32)

Consequence

FTO
NM_001080432.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.176

Publications

385 publications found

Variant links:

Genes affected

FTO (HGNC:24678): (FTO alpha-ketoglutarate dependent dioxygenase) This gene is a nuclear protein of the AlkB related non-haem iron and 2-oxoglutarate-dependent oxygenase superfamily but the exact physiological function of this gene is not known. Other non-heme iron enzymes function to reverse alkylated DNA and RNA damage by oxidative demethylation. Studies in mice and humans indicate a role in nervous and cardiovascular systems and a strong association with body mass index, obesity risk, and type 2 diabetes. [provided by RefSeq, Jul 2011]

FTO Gene-Disease associations (from GenCC):

lethal polymalformative syndrome, Boissel type
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae)

FTO links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001080432.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -14 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BP6

ClinVar 1-star benign — moderate (BP6); ClinVar germline classification: Benign/Likely Benign, 1 star(s).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.4040 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001080432.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FTO	NM_001080432.3	MANE Select	c.46-30685T>G	intron	N/A	NP_001073901.1	Q9C0B1-1
FTO	NM_001363894.2		c.46-30685T>G	intron	N/A	NP_001350823.1
FTO	NM_001363891.2		c.46-30685T>G	intron	N/A	NP_001350820.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FTO	ENST00000471389.6	TSL:1 MANE Select	c.46-30685T>G	intron	N/A	ENSP00000418823.1	Q9C0B1-1
FTO	ENST00000637969.1	TSL:5	c.46-30685T>G	intron	N/A	ENSP00000490516.1	A0A1B0GVH5
FTO	ENST00000918264.1		c.46-30685T>G	intron	N/A	ENSP00000588323.1

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58339

AN:

151908

Hom.:

11489

Cov.:

show subpopulations

Gnomad AFR

AF:

0.394

Gnomad AMI

AF:

0.462

Gnomad AMR

AF:

0.307

Gnomad ASJ

AF:

0.505

Gnomad EAS

AF:

0.152

Gnomad SAS

AF:

0.316

Gnomad FIN

AF:

0.399

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.384

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

GnomAD4 genome

AF:

0.384

AC:

58367

AN:

152026

Hom.:

11497

Cov.:

AF XY:

0.381

AC XY:

28308

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.394

AC:

16348

AN:

41454

American (AMR)

AF:

0.306

AC:

4682

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.505

AC:

1750

AN:

3466

East Asian (EAS)

AF:

0.152

AC:

785

AN:

5170

South Asian (SAS)

AF:

0.315

AC:

1521

AN:

4824

European-Finnish (FIN)

AF:

0.399

AC:

4215

AN:

10568

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.408

AC:

27722

AN:

67946

Other (OTH)

AF:

0.385

AC:

812

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1831

3662

5493

7324

9155

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

558

1116

1674

2232

2790

<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:

0.389

Hom.:

49735

Bravo

AF:

0.373

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.201

AC:

24701

AN:

122658

Turkish Variome

AF:

0.387

AC:

599

AN:

1546

Hom.:

128

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.124

AC:

1109

AN:

8960

Hom.:

ABraOM SABE-WGS-1171

AF:

0.404

AC:

946

AN:

2342

Hom.:

213

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.9

(source)

DANN

Benign

0.65

PhyloP100

-0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over