rs8177224

chr3-133755159-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.503-204C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,148 control chromosomes in the GnomAD database, including 6,853 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 0.29 (6853 hom., cov: 33)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334

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 = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TF	NM_001063.4	c.503-204C>G		intron_variant		ENST00000402696.9
TF	NM_001354703.2	c.371-204C>G		intron_variant
TF	NM_001354704.2	c.122-204C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TF	ENST00000402696.9	c.503-204C>G		intron_variant		1	NM_001063.4	P1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43811 AN: 152030 Hom.: 6851 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.288 AC: 43835 AN: 152148 Hom.: 6853 Cov.: 33 AF XY: 0.290 AC XY: 21589 AN XY: 74366

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.281

Alfa AF: 0.299 Hom.: 976

Bravo AF: 0.287

Asia WGS AF: 0.411 AC: 1428 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	0.40
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: rs8177224; hg19: chr3-133474003; COSMIC: COSV53918795; COSMIC: COSV53918795;