rs8177179

Variant names:

• chr3-133744613-G-A
• rs8177179
• NM_001354703.2:c.-89-3799G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001354703.2(TF):​c.-89-3799G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 151,960 control chromosomes in the GnomAD database, including 26,455 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 0.58 (26455 hom., cov: 32)
• Consequence: TF NM_001354703.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 11 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, MODERATE, SUPPORTIVE, LIMITED Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354703.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	NM_001354703.2		c.-89-3799G>A		intron	N/A	NP_001341632.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000291042	ENST00000460564.5	TSL:4	n.382-8982G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88709 AN: 151842 Hom.: 26416 Cov.: 32

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.584 AC: 88800 AN: 151960 Hom.: 26455 Cov.: 32 AF XY: 0.586 AC XY: 43499 AN XY: 74272

African (AFR) AF: 0.649 AC: 26887 AN: 41436

American (AMR) AF: 0.637 AC: 9731 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1773 AN: 3468

East Asian (EAS) AF: 0.759 AC: 3916 AN: 5160

South Asian (SAS) AF: 0.702 AC: 3373 AN: 4806

European-Finnish (FIN) AF: 0.501 AC: 5290 AN: 10552

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36194 AN: 67946

Other (OTH) AF: 0.556 AC: 1173 AN: 2110

Alfa AF: 0.571 Hom.: 3494

Bravo AF: 0.597

Asia WGS AF: 0.756 AC: 2629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.17
DANN	Benign	0.61
PhyloP100		-1.9

Splicing

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

Other links and lift over

dbSNP: rs8177179; hg19: chr3-133463457;