NM_001080432.3:c.45+41961C>T

Variant names:

• chr16-53746190-C-T
• rs7186637
• NM_001080432.3:c.45+41961C>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.45+41961C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,020 control chromosomes in the GnomAD database, including 5,209 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 0.25 (5209 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.606
• 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

LOC124903691 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 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.45+41961C>T		intron	N/A	NP_001073901.1
	FTO	NM_001363894.2		c.45+41961C>T		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.45+41961C>T		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.45+41961C>T		intron	N/A	ENSP00000418823.1
	FTO	ENST00000637969.1	TSL:5	c.45+41961C>T		intron	N/A	ENSP00000490516.1
	FTO	ENST00000637001.1	TSL:5	c.45+41961C>T		intron	N/A	ENSP00000489936.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37345 AN: 151902 Hom.: 5198 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.246 AC: 37388 AN: 152020 Hom.: 5209 Cov.: 32 AF XY: 0.241 AC XY: 17899 AN XY: 74300

African (AFR) AF: 0.378 AC: 15678 AN: 41432

American (AMR) AF: 0.158 AC: 2410 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 789 AN: 3472

East Asian (EAS) AF: 0.296 AC: 1529 AN: 5164

South Asian (SAS) AF: 0.233 AC: 1123 AN: 4818

European-Finnish (FIN) AF: 0.161 AC: 1699 AN: 10568

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13389 AN: 67986

Other (OTH) AF: 0.247 AC: 521 AN: 2110

Alfa AF: 0.224 Hom.: 6589

Bravo AF: 0.250

Asia WGS AF: 0.269 AC: 933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.96
PhyloP100		0.61
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: rs7186637; hg19: chr16-53780102;