rs16840699

Positions:

• chr3-133718757-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.-90+5576C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0899 in 152,156 control chromosomes in the GnomAD database, including 829 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 0.090 (829 hom., cov: 32)
• Consequence: TF NM_001354703.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TF	NM_001354703.2	c.-90+5576C>T		intron_variant			NP_001341632.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000291042	ENST00000460564.5	n.381+17704C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0897 AC: 13637 AN: 152038 Hom.: 820 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0210

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0519

Gnomad OTH AF: 0.0924

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

GnomAD4 genome AF: 0.0899 AC: 13673 AN: 152156 Hom.: 829 Cov.: 32 AF XY: 0.0900 AC XY: 6696 AN XY: 74378

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0620

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.0210

Gnomad4 NFE AF: 0.0519

Gnomad4 OTH AF: 0.0986

Alfa AF: 0.0738 Hom.: 123

Bravo AF: 0.100

Asia WGS AF: 0.196 AC: 679 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	2.9
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16840699; hg19: chr3-133437601;