3-133757483-T-C

Position:

• chr3-133757483-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001063.4(TF):​c.871-286T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,184 control chromosomes in the GnomAD database, including 49,810 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 0.81 (49810 hom., cov: 32)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TF	NM_001063.4	c.871-286T>C		intron_variant		ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.739-286T>C		intron_variant			NP_001341632.2
TF	NM_001354704.2	c.490-286T>C		intron_variant			NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.871-286T>C		intron_variant		1	NM_001063.4	ENSP00000385834.3
TF	ENST00000485977.1	n.236-286T>C		intron_variant		3		ENSP00000418716.1

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122453 AN: 152066 Hom.: 49729 Cov.: 32

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.806 AC: 122591 AN: 152184 Hom.: 49810 Cov.: 32 AF XY: 0.807 AC XY: 60044 AN XY: 74388

Gnomad4 AFR AF: 0.909

Gnomad4 AMR AF: 0.823

Gnomad4 ASJ AF: 0.766

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.864

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.746

Gnomad4 OTH AF: 0.784

Alfa AF: 0.786 Hom.: 11511

Bravo AF: 0.818

Asia WGS AF: 0.870 AC: 3025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs7645538; hg19: chr3-133476327;