3-133757483-T-C

Variant names:

• chr3-133757483-T-C
• rs7645538
• NM_001063.4:c.871-286T>C

Variant summary

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

The ENST00000402696.9(TF):​c.871-286T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,184 control chromosomes in the GnomAD database, including 49,810 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 0.81 (49810 hom., cov: 32)
• Consequence: TF ENST00000402696.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000402696.9. 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.871-286T>C		intron	N/A	NP_001054.2
	TF	NM_001354703.2		c.739-286T>C		intron	N/A	NP_001341632.2
	TF	NM_001354704.2		c.490-286T>C		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.871-286T>C		intron	N/A	ENSP00000385834.3
	TF	ENST00000485977.1	TSL:3	n.236-286T>C		intron	N/A	ENSP00000418716.1

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122453 AN: 152066 Hom.: 49729 Cov.: 32

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.806 AC: 122591 AN: 152184 Hom.: 49810 Cov.: 32 AF XY: 0.807 AC XY: 60044 AN XY: 74388

African (AFR) AF: 0.909 AC: 37743 AN: 41544

American (AMR) AF: 0.823 AC: 12585 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2656 AN: 3466

East Asian (EAS) AF: 0.911 AC: 4690 AN: 5148

South Asian (SAS) AF: 0.864 AC: 4170 AN: 4824

European-Finnish (FIN) AF: 0.710 AC: 7509 AN: 10580

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.746 AC: 50738 AN: 68004

Other (OTH) AF: 0.784 AC: 1658 AN: 2116

Alfa AF: 0.789 Hom.: 11826

Bravo AF: 0.818

Asia WGS AF: 0.870 AC: 3025 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	4.5
DANN	Benign	0.35
PhyloP100		-0.58
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: rs7645538; hg19: chr3-133476327;