rs1525892

Positions:

• chr3-133765868-G-A
• chr3-133765868-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.1331-410G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 149,070 control chromosomes in the GnomAD database, including 7,951 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 0.32 (7951 hom., cov: 32)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.540

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 (SAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TF	NM_001063.4	c.1331-410G>A		intron_variant		ENST00000402696.9
TF	NM_001354703.2	c.1199-410G>A		intron_variant
TF	NM_001354704.2	c.950-410G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TF	ENST00000402696.9	c.1331-410G>A		intron_variant		1	NM_001063.4	P1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 47885 AN: 148962 Hom.: 7943 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.322 AC: 47927 AN: 149070 Hom.: 7951 Cov.: 32 AF XY: 0.322 AC XY: 23470 AN XY: 72876

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.322

Alfa AF: 0.217 Hom.: 551

Bravo AF: 0.319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.32

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: rs1525892; hg19: chr3-133484712;