16-53821379-A-T

Variant names:

• chr16-53821379-A-T
• rs11075995
• NM_001080432.3:c.124-4485A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001080432.3(FTO):​c.124-4485A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 152,082 control chromosomes in the GnomAD database, including 45,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.77 (45063 hom., cov: 32)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.507
• Publications: 86 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-53821379-A-T is Benign according to our data. Variant chr16-53821379-A-T is described in ClinVar as Benign. ClinVar VariationId is 225825.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.817 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.124-4485A>T		intron	N/A	NP_001073901.1
	FTO	NM_001363894.2		c.124-4485A>T		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.124-4485A>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.124-4485A>T		intron	N/A	ENSP00000418823.1
	FTO	ENST00000637969.1	TSL:5	c.124-4485A>T		intron	N/A	ENSP00000490516.1
	FTO	ENST00000637001.1	TSL:5	c.124-4485A>T		intron	N/A	ENSP00000489936.1

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116905 AN: 151966 Hom.: 45017 Cov.: 32

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.762

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

GnomAD4 genome AF: 0.769 AC: 117004 AN: 152082 Hom.: 45063 Cov.: 32 AF XY: 0.766 AC XY: 56924 AN XY: 74326

African (AFR) AF: 0.824 AC: 34182 AN: 41492

American (AMR) AF: 0.698 AC: 10661 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2552 AN: 3470

East Asian (EAS) AF: 0.687 AC: 3554 AN: 5172

South Asian (SAS) AF: 0.764 AC: 3670 AN: 4802

European-Finnish (FIN) AF: 0.707 AC: 7476 AN: 10570

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.770 AC: 52320 AN: 67988

Other (OTH) AF: 0.762 AC: 1610 AN: 2112

Alfa AF: 0.762 Hom.: 5458

Bravo AF: 0.768

Asia WGS AF: 0.727 AC: 2529 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.49
DANN	Benign	0.61
PhyloP100		-0.51
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: rs11075995; hg19: chr16-53855291;