3-133757577-C-G

Variant names:

• chr3-133757577-C-G
• rs8177237
• NM_001063.4:c.871-192C>G

Variant summary

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

The NM_001063.4(TF):​c.871-192C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,086 control chromosomes in the GnomAD database, including 21,204 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 (21204 hom., cov: 33)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396
• Publications: 2 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, MODERATE, SUPPORTIVE, LIMITED Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.645 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	NM_001063.4	MANE Select	c.871-192C>G		intron	N/A	NP_001054.2	P02787
	TF	NM_001354703.2		c.739-192C>G		intron	N/A	NP_001341632.2
	TF	NM_001354704.2		c.490-192C>G		intron	N/A	NP_001341633.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	ENST00000402696.9	TSL:1 MANE Select	c.871-192C>G		intron	N/A	ENSP00000385834.3	P02787
	TF	ENST00000877249.1		c.223-192C>G		intron	N/A	ENSP00000547308.1
	TF	ENST00000877246.1		c.217-6605C>G		intron	N/A	ENSP00000547305.1

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78599 AN: 151968 Hom.: 21173 Cov.: 33

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.517 AC: 78676 AN: 152086 Hom.: 21204 Cov.: 33 AF XY: 0.524 AC XY: 38978 AN XY: 74346

African (AFR) AF: 0.364 AC: 15084 AN: 41490

American (AMR) AF: 0.612 AC: 9363 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1880 AN: 3468

East Asian (EAS) AF: 0.663 AC: 3422 AN: 5158

South Asian (SAS) AF: 0.649 AC: 3129 AN: 4822

European-Finnish (FIN) AF: 0.597 AC: 6312 AN: 10566

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37807 AN: 67972

Other (OTH) AF: 0.515 AC: 1085 AN: 2108

Alfa AF: 0.411 Hom.: 1175

Bravo AF: 0.510

Asia WGS AF: 0.652 AC: 2264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.52
PhyloP100		0.40
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: rs8177237; hg19: chr3-133476421;