3-133756719-G-T

Variant names:

• chr3-133756719-G-T
• rs4241357
• NM_001063.4:c.692-112G>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.692-112G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 1,361,964 control chromosomes in the GnomAD database, including 161,442 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 0.52 (21777 hom., cov: 32)
  • Exomes 𝑓: 0.47 (139665 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• 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, 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 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.692-112G>T		intron	N/A	NP_001054.2
	TF	NM_001354703.2		c.560-112G>T		intron	N/A	NP_001341632.2
	TF	NM_001354704.2		c.311-112G>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.692-112G>T		intron	N/A	ENSP00000385834.3
	TF	ENST00000482271.5	TSL:4	c.311-112G>T		intron	N/A	ENSP00000419338.1
	TF	ENST00000485977.1	TSL:3	n.158-213G>T		intron	N/A	ENSP00000418716.1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79455 AN: 151856 Hom.: 21733 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.490

GnomAD4 exome AF: 0.470 AC: 569186 AN: 1209990 Hom.: 139665 AF XY: 0.475 AC XY: 290825 AN XY: 612162

African (AFR) AF: 0.656 AC: 18744 AN: 28562

American (AMR) AF: 0.616 AC: 26877 AN: 43604

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 9416 AN: 24206

East Asian (EAS) AF: 0.744 AC: 28627 AN: 38476

South Asian (SAS) AF: 0.661 AC: 52954 AN: 80068

European-Finnish (FIN) AF: 0.474 AC: 22633 AN: 47758

Middle Eastern (MID) AF: 0.392 AC: 1467 AN: 3742

European-Non Finnish (NFE) AF: 0.430 AC: 383489 AN: 891530

Other (OTH) AF: 0.480 AC: 24979 AN: 52044

GnomAD4 genome AF: 0.524 AC: 79564 AN: 151974 Hom.: 21777 Cov.: 32 AF XY: 0.528 AC XY: 39203 AN XY: 74282

African (AFR) AF: 0.653 AC: 27054 AN: 41450

American (AMR) AF: 0.539 AC: 8225 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1334 AN: 3466

East Asian (EAS) AF: 0.737 AC: 3800 AN: 5154

South Asian (SAS) AF: 0.675 AC: 3251 AN: 4816

European-Finnish (FIN) AF: 0.478 AC: 5034 AN: 10534

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29326 AN: 67966

Other (OTH) AF: 0.497 AC: 1048 AN: 2110

Alfa AF: 0.463 Hom.: 21979

Bravo AF: 0.534

Asia WGS AF: 0.724 AC: 2513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.2
DANN	Benign	0.66
PhyloP100		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4241357; hg19: chr3-133475563; COSMIC: COSV53920793; COSMIC: COSV53920793;