rs4459901

Variant names:

• chr3-133746855-T-C
• rs4459901
• NM_001063.4:c.43+372T>C

Variant summary

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

The NM_001063.4(TF):​c.43+372T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,100 control chromosomes in the GnomAD database, including 9,580 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 0.35 (9580 hom., cov: 32)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760
• 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

ENSG00000291042 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4	c.43+372T>C		intron_variant	Intron 1 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.-89-1557T>C		intron_variant	Intron 7 of 22		NP_001341632.2
TF	NM_001354704.2	c.-166+372T>C		intron_variant	Intron 1 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.43+372T>C		intron_variant	Intron 1 of 16	1	NM_001063.4	ENSP00000385834.3

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53119 AN: 151982 Hom.: 9579 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.349 AC: 53147 AN: 152100 Hom.: 9580 Cov.: 32 AF XY: 0.349 AC XY: 25942 AN XY: 74340

African (AFR) AF: 0.396 AC: 16439 AN: 41464

American (AMR) AF: 0.375 AC: 5732 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3468

East Asian (EAS) AF: 0.413 AC: 2133 AN: 5160

South Asian (SAS) AF: 0.401 AC: 1937 AN: 4826

European-Finnish (FIN) AF: 0.305 AC: 3232 AN: 10580

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21870 AN: 67990

Other (OTH) AF: 0.319 AC: 674 AN: 2114

Alfa AF: 0.336 Hom.: 11634

Bravo AF: 0.356

Asia WGS AF: 0.428 AC: 1486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.41
PhyloP100		-0.76
PromoterAI		0.058	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs4459901; hg19: chr3-133465699; COSMIC: COSV53918754; COSMIC: COSV53918754;