rs1867504

Positions:

• chr3-133691817-A-G

Variant summary

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

The NM_001354703.2(TF):​c.-940+3453A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,316 control chromosomes in the GnomAD database, including 27,859 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 0.60 (27749 hom., cov: 33)
  • Exomes 𝑓: 0.49 (110 hom.)
• Consequence: TF NM_001354703.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21

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]

INHCAP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TF	NM_001354703.2	c.-940+3453A>G		intron_variant			NP_001341632.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INHCAP	ENST00000475455.1	n.268A>G		non_coding_transcript_exon_variant	2/10	6
ENSG00000291042	ENST00000460564.5	n.209+3453A>G		intron_variant		4
ENSG00000291042	ENST00000490470.5	n.209+3453A>G		intron_variant		4
ENSG00000291042	ENST00000497521.5	n.208+3453A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90361 AN: 151332 Hom.: 27705 Cov.: 33

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.579

GnomAD4 exome AF: 0.488 AC: 422 AN: 864 Hom.: 110 Cov.: 0 AF XY: 0.478 AC XY: 255 AN XY: 534

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.528

Gnomad4 NFE exome AF: 0.424

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.597 AC: 90464 AN: 151452 Hom.: 27749 Cov.: 33 AF XY: 0.598 AC XY: 44265 AN XY: 74000

Gnomad4 AFR AF: 0.743

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.578

Alfa AF: 0.539 Hom.: 33843

Bravo AF: 0.605

Asia WGS AF: 0.548 AC: 1906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.3
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1867504; hg19: chr3-133410661;