rs4428180

Variant names:

• chr3-133747530-A-G
• rs4428180
• NM_001063.4:c.44-882A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-133747530-A-G
• chr3-133747530-A-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.44-882A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,190 control chromosomes in the GnomAD database, including 1,904 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 0.15 (1904 hom., cov: 32)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 10 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

ENSG00000291042 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4	c.44-882A>G		intron_variant	Intron 1 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.-89-882A>G		intron_variant	Intron 7 of 22		NP_001341632.2
TF	NM_001354704.2	c.-166+1047A>G		intron_variant	Intron 1 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.44-882A>G		intron_variant	Intron 1 of 16	1	NM_001063.4	ENSP00000385834.3

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23314 AN: 152072 Hom.: 1897 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.153 AC: 23343 AN: 152190 Hom.: 1904 Cov.: 32 AF XY: 0.154 AC XY: 11426 AN XY: 74406

African (AFR) AF: 0.143 AC: 5937 AN: 41538

American (AMR) AF: 0.199 AC: 3043 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 599 AN: 3470

East Asian (EAS) AF: 0.269 AC: 1390 AN: 5160

South Asian (SAS) AF: 0.178 AC: 857 AN: 4820

European-Finnish (FIN) AF: 0.111 AC: 1180 AN: 10588

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9782 AN: 67998

Other (OTH) AF: 0.159 AC: 337 AN: 2114

Alfa AF: 0.151 Hom.: 2980

Bravo AF: 0.160

Asia WGS AF: 0.239 AC: 828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.5
DANN	Benign	0.74
PhyloP100		0.023
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4428180; hg19: chr3-133466374;