chr16-53956611-A-G

Variant names:

• chr16-53956611-A-G
• rs7191513
• NM_001080432.3:c.1364+22502A>G

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+22502A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 151,758 control chromosomes in the GnomAD database, including 20,432 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 0.51 (20430 hom., cov: 30)
  • Exomes 𝑓: 0.75 (2 hom.)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 11 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 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.1364+22502A>G		intron	N/A	NP_001073901.1	Q9C0B1-1
	FTO	NM_001363894.2		c.1427+22502A>G		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.1394+22502A>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.1364+22502A>G		intron	N/A	ENSP00000418823.1	Q9C0B1-1
	FTO	ENST00000268349.7	TSL:1	c.80+22502A>G		intron	N/A	ENSP00000268349.7	X6R3I0
	FTO	ENST00000463855.1	TSL:1	c.230+22502A>G		intron	N/A	ENSP00000417843.1	Q9C0B1-2

Frequencies

GnomAD3 genomes AF: 0.514 AC: 77976 AN: 151634 Hom.: 20432 Cov.: 30

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.546

GnomAD4 exome AF: 0.750 AC: 6 AN: 8 Hom.: 2 AF XY: 0.667 AC XY: 4 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 6 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.514 AC: 77999 AN: 151750 Hom.: 20430 Cov.: 30 AF XY: 0.510 AC XY: 37804 AN XY: 74164

African (AFR) AF: 0.456 AC: 18832 AN: 41306

American (AMR) AF: 0.566 AC: 8637 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1798 AN: 3468

East Asian (EAS) AF: 0.756 AC: 3899 AN: 5158

South Asian (SAS) AF: 0.453 AC: 2180 AN: 4810

European-Finnish (FIN) AF: 0.420 AC: 4409 AN: 10492

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

European-Non Finnish (NFE) AF: 0.534 AC: 36294 AN: 67946

Other (OTH) AF: 0.545 AC: 1148 AN: 2108

Alfa AF: 0.537 Hom.: 37106

Bravo AF: 0.527

Asia WGS AF: 0.561 AC: 1951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.35
DANN	Benign	0.82
PhyloP100		-1.1
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: rs7191513; hg19: chr16-53990523;