rs1880669

chr3-133764852-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001063.4(TF):c.1298-23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,609,006 control chromosomes in the GnomAD database, including 272,085 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 0.52 (21560 hom., cov: 33)
  • Exomes 𝑓: 0.58 (250525 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.705

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TF	NM_001063.4	c.1298-23T>C		intron_variant		ENST00000402696.9
TF	NM_001354703.2	c.1166-23T>C		intron_variant
TF	NM_001354704.2	c.917-23T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TF	ENST00000402696.9	c.1298-23T>C		intron_variant		1	NM_001063.4	P1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79468 AN: 151990 Hom.: 21550 Cov.: 33

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.536

GnomAD3 exomes AF: 0.565 AC: 141565 AN: 250474 Hom.: 40742 AF XY: 0.569 AC XY: 76916 AN XY: 135280

Gnomad AFR exome AF: 0.368

Gnomad AMR exome AF: 0.607

Gnomad ASJ exome AF: 0.512

Gnomad EAS exome AF: 0.460

Gnomad SAS exome AF: 0.586

Gnomad FIN exome AF: 0.614

Gnomad NFE exome AF: 0.588

Gnomad OTH exome AF: 0.555

GnomAD4 exome AF: 0.584 AC: 851055 AN: 1456898 Hom.: 250525 Cov.: 33 AF XY: 0.584 AC XY: 423369 AN XY: 724888

Gnomad4 AFR exome AF: 0.362

Gnomad4 AMR exome AF: 0.602

Gnomad4 ASJ exome AF: 0.512

Gnomad4 EAS exome AF: 0.507

Gnomad4 SAS exome AF: 0.581

Gnomad4 FIN exome AF: 0.609

Gnomad4 NFE exome AF: 0.595

Gnomad4 OTH exome AF: 0.566

GnomAD4 genome AF: 0.523 AC: 79500 AN: 152108 Hom.: 21560 Cov.: 33 AF XY: 0.523 AC XY: 38912 AN XY: 74374

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.535

Alfa AF: 0.572 Hom.: 43302

Bravo AF: 0.513

Asia WGS AF: 0.523 AC: 1817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	11
Dann	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1880669; hg19: chr3-133483696; COSMIC: COSV53917494; COSMIC: COSV53917494;