rs1880669

Variant names:

• chr3-133764852-T-C
• rs1880669
• NM_001063.4:c.1298-23T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001063.4(TF):​c.1298-23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,609,006 control chromosomes in the GnomAD database, including 272,085 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 0.52 (21560 hom., cov: 33)
  • Exomes 𝑓: 0.58 (250525 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.705
• Publications: 15 publications found

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]

TF Gene-Disease associations (from GenCC):

• atransferrinemia

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4	c.1298-23T>C		intron_variant	Intron 10 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.1166-23T>C		intron_variant	Intron 16 of 22		NP_001341632.2
TF	NM_001354704.2	c.917-23T>C		intron_variant	Intron 9 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.1298-23T>C		intron_variant	Intron 10 of 16	1	NM_001063.4	ENSP00000385834.3

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79468 AN: 151990 Hom.: 21550 Cov.: 33

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.536

GnomAD2 exomes AF: 0.565 AC: 141565 AN: 250474 AF XY: 0.569

Gnomad AFR exome AF: 0.368

Gnomad AMR exome AF: 0.607

Gnomad ASJ exome AF: 0.512

Gnomad EAS exome AF: 0.460

Gnomad FIN exome AF: 0.614

Gnomad NFE exome AF: 0.588

Gnomad OTH exome AF: 0.555

GnomAD4 exome AF: 0.584 AC: 851055 AN: 1456898 Hom.: 250525 Cov.: 33 AF XY: 0.584 AC XY: 423369 AN XY: 724888

African (AFR) AF: 0.362 AC: 12092 AN: 33366

American (AMR) AF: 0.602 AC: 26823 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 13359 AN: 26092

East Asian (EAS) AF: 0.507 AC: 20125 AN: 39658

South Asian (SAS) AF: 0.581 AC: 49810 AN: 85778

European-Finnish (FIN) AF: 0.609 AC: 32530 AN: 53398

Middle Eastern (MID) AF: 0.534 AC: 3069 AN: 5750

European-Non Finnish (NFE) AF: 0.595 AC: 659131 AN: 1108054

Other (OTH) AF: 0.566 AC: 34116 AN: 60224

GnomAD4 genome AF: 0.523 AC: 79500 AN: 152108 Hom.: 21560 Cov.: 33 AF XY: 0.523 AC XY: 38912 AN XY: 74374

African (AFR) AF: 0.368 AC: 15268 AN: 41470

American (AMR) AF: 0.563 AC: 8617 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1801 AN: 3470

East Asian (EAS) AF: 0.489 AC: 2531 AN: 5180

South Asian (SAS) AF: 0.565 AC: 2722 AN: 4814

European-Finnish (FIN) AF: 0.606 AC: 6413 AN: 10580

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40220 AN: 67972

Other (OTH) AF: 0.535 AC: 1130 AN: 2114

Alfa AF: 0.566 Hom.: 94599

Bravo AF: 0.513

Asia WGS AF: 0.523 AC: 1817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	11
DANN	Benign	0.93
PhyloP100		0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1880669; hg19: chr3-133483696; COSMIC: COSV53917494; COSMIC: COSV53917494;