rs7190492

Variant names:

• chr16-53794840-A-G
• rs7190492
• NM_001080432.3:c.46-15300A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-53794840-A-G
• chr16-53794840-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.46-15300A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 151,982 control chromosomes in the GnomAD database, including 35,456 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 0.68 (35456 hom., cov: 31)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.399
• Publications: 38 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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 = 0.783 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	NM_001080432.3	MANE Select	c.46-15300A>G		intron	N/A	NP_001073901.1	Q9C0B1-1
	FTO	NM_001363894.2		c.46-15300A>G		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.46-15300A>G		intron	N/A	NP_001350820.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	ENST00000471389.6	TSL:1 MANE Select	c.46-15300A>G		intron	N/A	ENSP00000418823.1	Q9C0B1-1
	FTO	ENST00000637969.1	TSL:5	c.46-15300A>G		intron	N/A	ENSP00000490516.1	A0A1B0GVH5
	FTO	ENST00000918264.1		c.46-15300A>G		intron	N/A	ENSP00000588323.1

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102850 AN: 151862 Hom.: 35402 Cov.: 31

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.677 AC: 102956 AN: 151982 Hom.: 35456 Cov.: 31 AF XY: 0.675 AC XY: 50143 AN XY: 74270

African (AFR) AF: 0.790 AC: 32731 AN: 41444

American (AMR) AF: 0.561 AC: 8566 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 2737 AN: 3468

East Asian (EAS) AF: 0.764 AC: 3934 AN: 5152

South Asian (SAS) AF: 0.680 AC: 3271 AN: 4810

European-Finnish (FIN) AF: 0.602 AC: 6351 AN: 10558

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 43066 AN: 67962

Other (OTH) AF: 0.685 AC: 1445 AN: 2110

Alfa AF: 0.652 Hom.: 88499

Bravo AF: 0.677

Asia WGS AF: 0.740 AC: 2571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.44
PhyloP100		-0.40
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: rs7190492; hg19: chr16-53828752;