3-133757577-C-G

Position:

• chr3-133757577-C-G

Variant summary

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

The NM_001063.4(TF):​c.871-192C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,086 control chromosomes in the GnomAD database, including 21,204 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 (21204 hom., cov: 33)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396

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 = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TF	NM_001063.4	c.871-192C>G		intron_variant		ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.739-192C>G		intron_variant			NP_001341632.2
TF	NM_001354704.2	c.490-192C>G		intron_variant			NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.871-192C>G		intron_variant		1	NM_001063.4	ENSP00000385834	P1
TF	ENST00000485977.1	c.236-192C>G		intron_variant, NMD_transcript_variant		3		ENSP00000418716

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78599 AN: 151968 Hom.: 21173 Cov.: 33

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.517 AC: 78676 AN: 152086 Hom.: 21204 Cov.: 33 AF XY: 0.524 AC XY: 38978 AN XY: 74346

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.663

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.597

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.515

Alfa AF: 0.411 Hom.: 1175

Bravo AF: 0.510

Asia WGS AF: 0.652 AC: 2264 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	4.8
DANN	Benign	0.52

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: rs8177237; hg19: chr3-133476421;