rs4525863

Variant names:

• chr3-133717292-C-A
• rs4525863
• NM_001354703.2:c.-90+4111C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-133717292-C-A
• chr3-133717292-C-G
• chr3-133717292-C-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+4111C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,954 control chromosomes in the GnomAD database, including 8,196 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 0.32 (8196 hom., cov: 31)
• Consequence: TF NM_001354703.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 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.-90+4111C>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.381+16239C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49191 AN: 151836 Hom.: 8194 Cov.: 31

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.324 AC: 49218 AN: 151954 Hom.: 8196 Cov.: 31 AF XY: 0.326 AC XY: 24211 AN XY: 74254

African (AFR) AF: 0.316 AC: 13094 AN: 41438

American (AMR) AF: 0.364 AC: 5557 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 844 AN: 3464

East Asian (EAS) AF: 0.415 AC: 2128 AN: 5130

South Asian (SAS) AF: 0.413 AC: 1986 AN: 4810

European-Finnish (FIN) AF: 0.306 AC: 3233 AN: 10552

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21448 AN: 67966

Other (OTH) AF: 0.301 AC: 637 AN: 2114

Alfa AF: 0.318 Hom.: 24989

Bravo AF: 0.327

Asia WGS AF: 0.432 AC: 1501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.74
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs4525863; hg19: chr3-133436136; COSMIC: COSV71704636;