rs4854761

Positions:

• chr3-133779945-G-A

Variant summary

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

The NM_001063.4(TF):​c.*1325G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,982 control chromosomes in the GnomAD database, including 8,536 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 0.33 (8536 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TF NM_001063.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TF	NM_001063.4	c.*1325G>A		3_prime_UTR_variant	17/17	ENST00000402696.9
TF	NM_001354703.2	c.*1325G>A		3_prime_UTR_variant	23/23
TF	NM_001354704.2	c.*1325G>A		3_prime_UTR_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TF	ENST00000402696.9	c.*1325G>A		3_prime_UTR_variant	17/17	1	NM_001063.4	P1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50032 AN: 151864 Hom.: 8528 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.325

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 AMR exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.329 AC: 50074 AN: 151982 Hom.: 8536 Cov.: 32 AF XY: 0.329 AC XY: 24465 AN XY: 74278

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.326

Alfa AF: 0.341 Hom.: 1927

Bravo AF: 0.335

Asia WGS AF: 0.398 AC: 1382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.52
DANN	Benign	0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4854761; hg19: chr3-133498789;