rs2718812

Positions:

• chr3-133680858-C-T

Variant summary

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

The NM_001354703.2(TF):​c.-1112-7334C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,922 control chromosomes in the GnomAD database, including 22,144 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 0.53 (22144 hom., cov: 31)
• Consequence: TF NM_001354703.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TF	NM_001354703.2	c.-1112-7334C>T		intron_variant			NP_001341632.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000291042	ENST00000460564.5	n.37-7334C>T		intron_variant		4
ENSG00000291042	ENST00000490470.5	n.37-7334C>T		intron_variant		4
ENSG00000291042	ENST00000497521.5	n.36-7334C>T		intron_variant		4
ENSG00000291042	ENST00000687252.2	n.109-7334C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80267 AN: 151804 Hom.: 22103 Cov.: 31

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.529 AC: 80370 AN: 151922 Hom.: 22144 Cov.: 31 AF XY: 0.530 AC XY: 39349 AN XY: 74240

Gnomad4 AFR AF: 0.691

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.503

Alfa AF: 0.463 Hom.: 37085

Bravo AF: 0.537

Asia WGS AF: 0.515 AC: 1793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.1
DANN	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2718812; hg19: chr3-133399702;