rs4854759

Variant names:

• chr3-133755101-T-G
• rs4854759
• NM_001063.4:c.503-262T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001063.4(TF):​c.503-262T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0852 in 152,268 control chromosomes in the GnomAD database, including 697 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 0.085 (697 hom., cov: 33)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• Publications: 2 publications found

Genes affected

TF (HGNC:11740): (transferrin) This gene encodes a glycoprotein with an approximate molecular weight of 76.5 kDa. It is thought to have been created as a result of an ancient gene duplication event that led to generation of homologous C and N-terminal domains each of which binds one ion of ferric iron. The function of this protein is to transport iron from the intestine, reticuloendothelial system, and liver parenchymal cells to all proliferating cells in the body. This protein may also have a physiologic role as granulocyte/pollen-binding protein (GPBP) involved in the removal of certain organic matter and allergens from serum. [provided by RefSeq, Sep 2009]

TF Gene-Disease associations (from GenCC):

• atransferrinemia

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4	c.503-262T>G		intron_variant	Intron 4 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.371-262T>G		intron_variant	Intron 10 of 22		NP_001341632.2
TF	NM_001354704.2	c.122-262T>G		intron_variant	Intron 3 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.503-262T>G		intron_variant	Intron 4 of 16	1	NM_001063.4	ENSP00000385834.3

Frequencies

GnomAD3 genomes AF: 0.0852 AC: 12967 AN: 152150 Hom.: 697 Cov.: 33

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.0310

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0772

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

GnomAD4 genome AF: 0.0852 AC: 12966 AN: 152268 Hom.: 697 Cov.: 33 AF XY: 0.0859 AC XY: 6395 AN XY: 74446

African (AFR) AF: 0.0259 AC: 1075 AN: 41566

American (AMR) AF: 0.102 AC: 1560 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 483 AN: 3472

East Asian (EAS) AF: 0.0311 AC: 161 AN: 5180

South Asian (SAS) AF: 0.0846 AC: 408 AN: 4822

European-Finnish (FIN) AF: 0.116 AC: 1235 AN: 10602

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7790 AN: 68008

Other (OTH) AF: 0.0769 AC: 162 AN: 2108

Alfa AF: 0.0907 Hom.: 228

Bravo AF: 0.0797

Asia WGS AF: 0.0540 AC: 187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.36
PhyloP100		-0.11
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: rs4854759; hg19: chr3-133473945;