rs1405022

Variant names:

• chr3-133762874-C-T
• rs1405022
• NM_001063.4:c.1204-1308C>T

Variant summary

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

The NM_001063.4(TF):​c.1204-1308C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 152,012 control chromosomes in the GnomAD database, including 20,821 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 0.51 (20821 hom., cov: 32)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460
• Publications: 2 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001063.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	NM_001063.4	MANE Select	c.1204-1308C>T		intron	N/A	NP_001054.2
	TF	NM_001354703.2		c.1072-1308C>T		intron	N/A	NP_001341632.2
	TF	NM_001354704.2		c.823-1308C>T		intron	N/A	NP_001341633.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	ENST00000402696.9	TSL:1 MANE Select	c.1204-1308C>T		intron	N/A	ENSP00000385834.3

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77450 AN: 151894 Hom.: 20813 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.510 AC: 77477 AN: 152012 Hom.: 20821 Cov.: 32 AF XY: 0.510 AC XY: 37902 AN XY: 74312

African (AFR) AF: 0.326 AC: 13498 AN: 41454

American (AMR) AF: 0.556 AC: 8494 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1806 AN: 3470

East Asian (EAS) AF: 0.493 AC: 2557 AN: 5182

South Asian (SAS) AF: 0.556 AC: 2682 AN: 4822

European-Finnish (FIN) AF: 0.604 AC: 6373 AN: 10556

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.591 AC: 40167 AN: 67944

Other (OTH) AF: 0.526 AC: 1106 AN: 2104

Alfa AF: 0.527 Hom.: 2868

Bravo AF: 0.499

Asia WGS AF: 0.517 AC: 1799 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	16
DANN	Benign	0.78
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1405022; hg19: chr3-133481718; COSMIC: COSV53918900; COSMIC: COSV53918900;