rs16840699

Variant names:

• chr3-133718757-C-T
• rs16840699
• NM_001354703.2:c.-90+5576C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.91).
• 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 rank	MANE	Protein	UniProt
TF	NM_001354703.2	c.-90+5576C>T		intron_variant	Intron 7 of 22		NP_001341632.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000291042	ENST00000460564.5	n.381+17704C>T		intron_variant	Intron 3 of 4	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

African (AFR) AF: 0.141 AC: 5856 AN: 41492

American (AMR) AF: 0.108 AC: 1646 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0620 AC: 215 AN: 3470

East Asian (EAS) AF: 0.261 AC: 1350 AN: 5170

South Asian (SAS) AF: 0.127 AC: 614 AN: 4822

European-Finnish (FIN) AF: 0.0210 AC: 223 AN: 10598

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0519 AC: 3529 AN: 67998

Other (OTH) AF: 0.0986 AC: 208 AN: 2110

Alfa AF: 0.0752 Hom.: 132

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
PhyloP100		-0.17

Splicing

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

Other links and lift over

dbSNP: rs16840699; hg19: chr3-133437601;