3-133765344-C-T

Variant names:

• chr3-133765344-C-T
• rs1358024
• NM_001063.4:c.1330+437C>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.1330+437C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,228 control chromosomes in the GnomAD database, including 2,057 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 0.14 (2057 hom., cov: 32)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350
• Publications: 15 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, PanelApp Australia, Orphanet, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	NM_001063.4	MANE Select	c.1330+437C>T		intron	N/A	NP_001054.2	P02787
	TF	NM_001354703.2		c.1198+437C>T		intron	N/A	NP_001341632.2
	TF	NM_001354704.2		c.949+437C>T		intron	N/A	NP_001341633.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	ENST00000402696.9	TSL:1 MANE Select	c.1330+437C>T		intron	N/A	ENSP00000385834.3	P02787
	TF	ENST00000877249.1		c.682+437C>T		intron	N/A	ENSP00000547308.1
	TF	ENST00000877246.1		c.343+437C>T		intron	N/A	ENSP00000547305.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21417 AN: 152110 Hom.: 2059 Cov.: 32

Gnomad AFR AF: 0.0331

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.141 AC: 21423 AN: 152228 Hom.: 2057 Cov.: 32 AF XY: 0.146 AC XY: 10883 AN XY: 74428

African (AFR) AF: 0.0332 AC: 1380 AN: 41556

American (AMR) AF: 0.195 AC: 2989 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 600 AN: 3472

East Asian (EAS) AF: 0.384 AC: 1987 AN: 5174

South Asian (SAS) AF: 0.283 AC: 1365 AN: 4824

European-Finnish (FIN) AF: 0.129 AC: 1367 AN: 10606

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11217 AN: 67986

Other (OTH) AF: 0.163 AC: 343 AN: 2108

Alfa AF: 0.163 Hom.: 4241

Bravo AF: 0.138

Asia WGS AF: 0.285 AC: 988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.3
DANN	Benign	0.59
PhyloP100		-0.35
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1358024;

hg19: chr3-133484188;

COSMIC: COSV53918933;

COSMIC: COSV53918933;