rs4481157

Positions:

• chr3-133745840-G-A

Variant summary

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

The NM_001354703.2(TF):​c.-89-2572G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 155,178 control chromosomes in the GnomAD database, including 13,240 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 0.41 (13089 hom., cov: 32)
  • Exomes 𝑓: 0.27 (151 hom.)
• Consequence: TF NM_001354703.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.596

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]

ENSG00000291042 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TF	NM_001354703.2	c.-89-2572G>A		intron_variant			NP_001341632.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000291042	ENST00000460564.5	n.382-7755G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62158 AN: 151894 Hom.: 13071 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.370

GnomAD4 exome AF: 0.268 AC: 847 AN: 3166 Hom.: 151 AF XY: 0.268 AC XY: 424 AN XY: 1582

Gnomad4 AFR exome AF: 0.467

Gnomad4 AMR exome AF: 0.293

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.400

Gnomad4 SAS exome AF: 0.285

Gnomad4 FIN exome AF: 0.271

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.254

GnomAD4 genome AF: 0.409 AC: 62225 AN: 152012 Hom.: 13089 Cov.: 32 AF XY: 0.412 AC XY: 30571 AN XY: 74284

Gnomad4 AFR AF: 0.478

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.370

Alfa AF: 0.397 Hom.: 1967

Bravo AF: 0.414

Asia WGS AF: 0.511 AC: 1777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.3
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4481157; hg19: chr3-133464684;