rs8177190

Variant names:

• chr3-133748852-C-T
• rs8177190
• NM_001063.4:c.216+268C>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.216+268C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0869 in 151,916 control chromosomes in the GnomAD database, including 719 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: 𝑓 0.087 (719 hom., cov: 31)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786
• 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, MODERATE, SUPPORTIVE, LIMITED Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 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.216+268C>T		intron	N/A	NP_001054.2	P02787
	TF	NM_001354703.2		c.84+268C>T		intron	N/A	NP_001341632.2
	TF	NM_001354704.2		c.-166+2369C>T		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.216+268C>T		intron	N/A	ENSP00000385834.3	P02787
	TF	ENST00000877249.1		c.43+2369C>T		intron	N/A	ENSP00000547308.1
	TF	ENST00000877246.1		c.216+268C>T		intron	N/A	ENSP00000547305.1

Frequencies

GnomAD3 genomes AF: 0.0870 AC: 13201 AN: 151798 Hom.: 719 Cov.: 31

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0306

Gnomad SAS AF: 0.0846

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0822

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

GnomAD4 genome AF: 0.0869 AC: 13201 AN: 151916 Hom.: 719 Cov.: 31 AF XY: 0.0874 AC XY: 6490 AN XY: 74250

African (AFR) AF: 0.0262 AC: 1087 AN: 41468

American (AMR) AF: 0.106 AC: 1620 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 592 AN: 3466

East Asian (EAS) AF: 0.0307 AC: 157 AN: 5122

South Asian (SAS) AF: 0.0847 AC: 406 AN: 4796

European-Finnish (FIN) AF: 0.114 AC: 1206 AN: 10554

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7839 AN: 67932

Other (OTH) AF: 0.0818 AC: 172 AN: 2102

Alfa AF: 0.110 Hom.: 1590

Bravo AF: 0.0823

Asia WGS AF: 0.0550 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.66
PhyloP100		-0.79
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: rs8177190; hg19: chr3-133467696;