16-54118818-A-G

Variant names:

• chr16-54118818-A-G
• rs2072518
• NM_001080432.3:c.*6903A>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.*6903A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,028 control chromosomes in the GnomAD database, including 10,779 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 0.36 (10775 hom., cov: 31)
  • Exomes 𝑓: 0.50 (4 hom.)
• Consequence: FTO NM_001080432.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56
• Publications: 16 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.*6903A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.*6903A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_001080432.3	ENSP00000418823.1
FTO	ENST00000637969.1	c.1492+6929A>G		intron_variant	Intron 9 of 10	5		ENSP00000490516.1
FTO	ENST00000612285.2	c.517+6929A>G		intron_variant	Intron 4 of 4	5		ENSP00000490300.1
FTO	ENST00000637845.1	n.*316+12A>G		intron_variant	Intron 10 of 10	5		ENSP00000489638.1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54573 AN: 151886 Hom.: 10770 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.359

GnomAD4 exome AF: 0.500 AC: 12 AN: 24 Hom.: 4 Cov.: 0 AF XY: 0.556 AC XY: 10 AN XY: 18

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

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

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.550 AC: 11 AN: 20

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.359 AC: 54601 AN: 152004 Hom.: 10775 Cov.: 31 AF XY: 0.366 AC XY: 27203 AN XY: 74244

African (AFR) AF: 0.190 AC: 7895 AN: 41474

American (AMR) AF: 0.392 AC: 5995 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1387 AN: 3468

East Asian (EAS) AF: 0.515 AC: 2659 AN: 5160

South Asian (SAS) AF: 0.386 AC: 1852 AN: 4804

European-Finnish (FIN) AF: 0.503 AC: 5297 AN: 10526

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28377 AN: 67968

Other (OTH) AF: 0.360 AC: 760 AN: 2114

Alfa AF: 0.395 Hom.: 9517

Bravo AF: 0.345

Asia WGS AF: 0.407 AC: 1412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.063
DANN	Benign	0.34
PhyloP100		-2.6
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: rs2072518; hg19: chr16-54152730;