3-133765344-C-T

Position:

• chr3-133765344-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TF	NM_001063.4	c.1330+437C>T		intron_variant		ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.1198+437C>T		intron_variant			NP_001341632.2
TF	NM_001354704.2	c.949+437C>T		intron_variant			NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.1330+437C>T		intron_variant		1	NM_001063.4	ENSP00000385834	P1

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

Gnomad4 AFR AF: 0.0332

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.163

Alfa AF: 0.166 Hom.: 3114

Bravo AF: 0.138

Asia WGS AF: 0.285 AC: 988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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: rs1358024; hg19: chr3-133484188; COSMIC: COSV53918933; COSMIC: COSV53918933;