3-133757117-A-G

Variant names:

• chr3-133757117-A-G
• rs8177233
• NM_001063.4:c.870+108A>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.870+108A>G variant causes a intron change. The variant allele was found at a frequency of 0.0131 in 1,427,962 control chromosomes in the GnomAD database, including 1,902 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 0.065 (1041 hom., cov: 32)
  • Exomes 𝑓: 0.0069 (861 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.59
• Publications: 1 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4	c.870+108A>G		intron_variant	Intron 7 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.738+108A>G		intron_variant	Intron 13 of 22		NP_001341632.2
TF	NM_001354704.2	c.489+108A>G		intron_variant	Intron 6 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.870+108A>G		intron_variant	Intron 7 of 16	1	NM_001063.4	ENSP00000385834.3
TF	ENST00000485977.1	n.235+108A>G		intron_variant	Intron 3 of 4	3		ENSP00000418716.1
TF	ENST00000482271.5	c.*194A>G		downstream_gene_variant		4		ENSP00000419338.1

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 9889 AN: 152038 Hom.: 1039 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0274

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000809

Gnomad OTH AF: 0.0468

GnomAD4 exome AF: 0.00688 AC: 8782 AN: 1275806 Hom.: 861 AF XY: 0.00590 AC XY: 3785 AN XY: 641356

African (AFR) AF: 0.233 AC: 6973 AN: 29868

American (AMR) AF: 0.0137 AC: 565 AN: 41324

Ashkenazi Jewish (ASJ) AF: 0.000448 AC: 11 AN: 24572

East Asian (EAS) AF: 0.00 AC: 0 AN: 38152

South Asian (SAS) AF: 0.000411 AC: 33 AN: 80226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50146

Middle Eastern (MID) AF: 0.0105 AC: 55 AN: 5262

European-Non Finnish (NFE) AF: 0.000367 AC: 349 AN: 951996

Other (OTH) AF: 0.0147 AC: 796 AN: 54260

GnomAD4 genome AF: 0.0651 AC: 9909 AN: 152156 Hom.: 1041 Cov.: 32 AF XY: 0.0636 AC XY: 4730 AN XY: 74408

African (AFR) AF: 0.225 AC: 9327 AN: 41448

American (AMR) AF: 0.0274 AC: 419 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000809 AC: 55 AN: 68014

Other (OTH) AF: 0.0464 AC: 98 AN: 2114

Alfa AF: 0.0406 Hom.: 200

Bravo AF: 0.0745

Asia WGS AF: 0.0130 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		3.6
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: rs8177233; hg19: chr3-133475961;