rs4784351

Variant names:

• chr16-54041786-A-G
• rs4784351
• NM_001080432.3:c.1365-69976A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-54041786-A-G
• chr16-54041786-A-T

Variant summary

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

The NM_001080432.3(FTO):​c.1365-69976A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 152,062 control chromosomes in the GnomAD database, including 17,284 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 0.44 (17284 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 10 publications found

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: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ENSG00000261049 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Variant Effect in Transcripts

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

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	NM_001080432.3	MANE Select	c.1365-69976A>G		intron	N/A	NP_001073901.1
	FTO	NM_001363894.2		c.1428-69976A>G		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.1395-69976A>G		intron	N/A	NP_001350820.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	ENST00000471389.6	TSL:1 MANE Select	c.1365-69976A>G		intron	N/A	ENSP00000418823.1
	FTO	ENST00000268349.7	TSL:1	c.97+56832A>G		intron	N/A	ENSP00000268349.7
	FTO	ENST00000463855.1	TSL:1	c.231-69976A>G		intron	N/A	ENSP00000417843.1

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66950 AN: 151944 Hom.: 17238 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.441 AC: 67051 AN: 152062 Hom.: 17284 Cov.: 32 AF XY: 0.447 AC XY: 33215 AN XY: 74328

African (AFR) AF: 0.707 AC: 29330 AN: 41492

American (AMR) AF: 0.433 AC: 6627 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 809 AN: 3468

East Asian (EAS) AF: 0.528 AC: 2723 AN: 5162

South Asian (SAS) AF: 0.408 AC: 1963 AN: 4814

European-Finnish (FIN) AF: 0.426 AC: 4494 AN: 10550

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19960 AN: 67970

Other (OTH) AF: 0.371 AC: 784 AN: 2114

Alfa AF: 0.330 Hom.: 40001

Bravo AF: 0.452

Asia WGS AF: 0.458 AC: 1590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.9
DANN	Benign	0.53
PhyloP100		1.0
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: rs4784351; hg19: chr16-54075698;