rs8177277

Variant names:

• chr3-133765986-T-C
• rs8177277
• NM_001063.4:c.1331-292T>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.1331-292T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0516 in 152,338 control chromosomes in the GnomAD database, including 277 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 0.052 (277 hom., cov: 33)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 8 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0699 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.1331-292T>C		intron	N/A	NP_001054.2	P02787
	TF	NM_001354703.2		c.1199-292T>C		intron	N/A	NP_001341632.2
	TF	NM_001354704.2		c.950-292T>C		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.1331-292T>C		intron	N/A	ENSP00000385834.3	P02787
	TF	ENST00000877249.1		c.683-292T>C		intron	N/A	ENSP00000547308.1
	TF	ENST00000877246.1		c.344-292T>C		intron	N/A	ENSP00000547305.1

Frequencies

GnomAD3 genomes AF: 0.0516 AC: 7857 AN: 152220 Hom.: 278 Cov.: 33

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0677

Gnomad ASJ AF: 0.0539

Gnomad EAS AF: 0.0225

Gnomad SAS AF: 0.0221

Gnomad FIN AF: 0.0752

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0716

Gnomad OTH AF: 0.0406

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

GnomAD4 genome AF: 0.0516 AC: 7857 AN: 152338 Hom.: 277 Cov.: 33 AF XY: 0.0520 AC XY: 3875 AN XY: 74494

African (AFR) AF: 0.0142 AC: 592 AN: 41594

American (AMR) AF: 0.0676 AC: 1035 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0539 AC: 187 AN: 3468

East Asian (EAS) AF: 0.0224 AC: 116 AN: 5186

South Asian (SAS) AF: 0.0219 AC: 106 AN: 4832

European-Finnish (FIN) AF: 0.0752 AC: 798 AN: 10616

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0716 AC: 4868 AN: 68022

Other (OTH) AF: 0.0407 AC: 86 AN: 2114

Alfa AF: 0.0542 Hom.: 158

Bravo AF: 0.0492

Asia WGS AF: 0.0240 AC: 82 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.29
DANN	Benign	0.44
PhyloP100		-1.4
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: rs8177277; hg19: chr3-133484830;