rs9940629

Variant names:

• chr16-53970899-A-G
• rs9940629
• NM_001080432.3:c.1364+36790A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-53970899-A-G
• chr16-53970899-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.1364+36790A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 152,080 control chromosomes in the GnomAD database, including 25,735 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 0.58 (25735 hom., cov: 33)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.541
• Publications: 14 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 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.1364+36790A>G		intron	N/A	NP_001073901.1
	FTO	NM_001363894.2		c.1427+36790A>G		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.1394+36790A>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.1364+36790A>G		intron	N/A	ENSP00000418823.1
	FTO	ENST00000268349.7	TSL:1	c.81-14039A>G		intron	N/A	ENSP00000268349.7
	FTO	ENST00000463855.1	TSL:1	c.230+36790A>G		intron	N/A	ENSP00000417843.1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87694 AN: 151962 Hom.: 25720 Cov.: 33

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.577 AC: 87762 AN: 152080 Hom.: 25735 Cov.: 33 AF XY: 0.573 AC XY: 42594 AN XY: 74352

African (AFR) AF: 0.555 AC: 23040 AN: 41500

American (AMR) AF: 0.654 AC: 9998 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1871 AN: 3464

East Asian (EAS) AF: 0.827 AC: 4267 AN: 5158

South Asian (SAS) AF: 0.482 AC: 2325 AN: 4822

European-Finnish (FIN) AF: 0.448 AC: 4731 AN: 10570

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39430 AN: 67974

Other (OTH) AF: 0.606 AC: 1274 AN: 2104

Alfa AF: 0.589 Hom.: 80851

Bravo AF: 0.597

Asia WGS AF: 0.633 AC: 2201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.24
DANN	Benign	0.33
PhyloP100		-0.54
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: rs9940629; hg19: chr16-54004811;