rs56137030

Variant names:

• chr16-53791993-G-A
• rs56137030
• NM_001080432.3:c.46-18147G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-53791993-G-A
• chr16-53791993-G-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.46-18147G>A variant causes a intron change. The variant allele was found at a frequency of 0.301 in 151,504 control chromosomes in the GnomAD database, including 8,309 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 0.30 (8309 hom., cov: 30)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: No conservation score assigned
• Publications: 18 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 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.46-18147G>A		intron	N/A	NP_001073901.1
	FTO	NM_001363894.2		c.46-18147G>A		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.46-18147G>A		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.46-18147G>A		intron	N/A	ENSP00000418823.1
	FTO	ENST00000637969.1	TSL:5	c.46-18147G>A		intron	N/A	ENSP00000490516.1
	FTO	ENST00000637001.1	TSL:5	c.46-18147G>A		intron	N/A	ENSP00000489936.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45677 AN: 151384 Hom.: 8311 Cov.: 30

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.378

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.301 AC: 45667 AN: 151504 Hom.: 8309 Cov.: 30 AF XY: 0.301 AC XY: 22309 AN XY: 74020

African (AFR) AF: 0.106 AC: 4392 AN: 41382

American (AMR) AF: 0.276 AC: 4195 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1736 AN: 3466

East Asian (EAS) AF: 0.154 AC: 791 AN: 5136

South Asian (SAS) AF: 0.313 AC: 1502 AN: 4800

European-Finnish (FIN) AF: 0.401 AC: 4161 AN: 10366

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.408 AC: 27679 AN: 67832

Other (OTH) AF: 0.326 AC: 683 AN: 2098

Alfa AF: 0.225 Hom.: 627

Bravo AF: 0.280

Asia WGS AF: 0.269 AC: 937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.7
DANN	Benign	0.96
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: rs56137030; hg19: chr16-53825905;