16-53824112-C-T

Variant names:

• chr16-53824112-C-T
• rs11075996
• NM_001080432.3:c.124-1752C>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.124-1752C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,020 control chromosomes in the GnomAD database, including 11,440 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 0.38 (11440 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 13 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 (AMR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3	c.124-1752C>T		intron_variant	Intron 2 of 8	ENST00000471389.6	NP_001073901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTO	ENST00000471389.6	c.124-1752C>T		intron_variant	Intron 2 of 8	1	NM_001080432.3	ENSP00000418823.1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57804 AN: 151900 Hom.: 11433 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.381 AC: 57844 AN: 152020 Hom.: 11440 Cov.: 32 AF XY: 0.376 AC XY: 27916 AN XY: 74308

African (AFR) AF: 0.356 AC: 14741 AN: 41456

American (AMR) AF: 0.436 AC: 6657 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1711 AN: 3468

East Asian (EAS) AF: 0.235 AC: 1213 AN: 5160

South Asian (SAS) AF: 0.407 AC: 1962 AN: 4822

European-Finnish (FIN) AF: 0.221 AC: 2332 AN: 10564

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27718 AN: 67968

Other (OTH) AF: 0.412 AC: 872 AN: 2114

Alfa AF: 0.404 Hom.: 27003

Bravo AF: 0.391

Asia WGS AF: 0.346 AC: 1204 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	3.2
DANN	Benign	0.68
PhyloP100		0.30
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: rs11075996; hg19: chr16-53858024;