rs1800277

Variant names:

• chr3-133747311-C-T
• rs1800277
• NM_001063.4:c.43+828C>T

Variant summary

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

The NM_001063.4(TF):​c.43+828C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 152,420 control chromosomes in the GnomAD database, including 445 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 0.069 (445 hom., cov: 33)
  • Exomes 𝑓: 0.079 (0 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330
• Publications: 5 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

ENSG00000291042 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 = 0.115 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001063.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	NM_001063.4	MANE Select	c.43+828C>T		intron	N/A	NP_001054.2
	TF	NM_001354703.2		c.-89-1101C>T		intron	N/A	NP_001341632.2
	TF	NM_001354704.2		c.-166+828C>T		intron	N/A	NP_001341633.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	ENST00000402696.9	TSL:1 MANE Select	c.43+828C>T		intron	N/A	ENSP00000385834.3
	TF	ENST00000482271.5	TSL:4	c.-166+828C>T		intron	N/A	ENSP00000419338.1
	TF	ENST00000466911.5	TSL:4	c.-90+1062C>T		intron	N/A	ENSP00000417468.1

Frequencies

GnomAD3 genomes AF: 0.0690 AC: 10504 AN: 152188 Hom.: 440 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0443

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0835

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0485

Gnomad OTH AF: 0.0583

GnomAD4 exome AF: 0.0789 AC: 9 AN: 114 Hom.: 0 Cov.: 0 AF XY: 0.0667 AC XY: 6 AN XY: 90

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0900 AC: 9 AN: 100

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0692 AC: 10538 AN: 152306 Hom.: 445 Cov.: 33 AF XY: 0.0708 AC XY: 5277 AN XY: 74484

African (AFR) AF: 0.105 AC: 4381 AN: 41556

American (AMR) AF: 0.0442 AC: 677 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0778 AC: 270 AN: 3472

East Asian (EAS) AF: 0.0530 AC: 275 AN: 5186

South Asian (SAS) AF: 0.124 AC: 597 AN: 4830

European-Finnish (FIN) AF: 0.0835 AC: 886 AN: 10616

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0485 AC: 3300 AN: 68020

Other (OTH) AF: 0.0591 AC: 125 AN: 2114

Alfa AF: 0.0553 Hom.: 340

Bravo AF: 0.0675

Asia WGS AF: 0.0830 AC: 290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.6
DANN	Benign	0.43
PhyloP100		0.033
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1800277; hg19: chr3-133466155;