chr3-133756719-G-T

Position:

• chr3-133756719-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TF	NM_001063.4	c.692-112G>T		intron_variant		ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.560-112G>T		intron_variant			NP_001341632.2
TF	NM_001354704.2	c.311-112G>T		intron_variant			NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.692-112G>T		intron_variant		1	NM_001063.4	ENSP00000385834.3
TF	ENST00000482271.5	c.311-112G>T		intron_variant		4		ENSP00000419338.1
TF	ENST00000485977.1	n.158-213G>T		intron_variant		3		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

Gnomad4 AFR exome AF: 0.656

Gnomad4 AMR exome AF: 0.616

Gnomad4 ASJ exome AF: 0.389

Gnomad4 EAS exome AF: 0.744

Gnomad4 SAS exome AF: 0.661

Gnomad4 FIN exome AF: 0.474

Gnomad4 NFE exome AF: 0.430

Gnomad4 OTH exome AF: 0.480

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

Gnomad4 AFR AF: 0.653

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.497

Alfa AF: 0.453 Hom.: 16132

Bravo AF: 0.534

Asia WGS AF: 0.724 AC: 2513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.2
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4241357; hg19: chr3-133475563; COSMIC: COSV53920793; COSMIC: COSV53920793;