chr3-133744428-G-A

Variant names:

• chr3-133744428-G-A
• rs8177178
• NM_001354703.2:c.-89-3984G>A

Variant summary

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

The NM_001354703.2(TF):​c.-89-3984G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,112 control chromosomes in the GnomAD database, including 8,622 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 0.33 (8622 hom., cov: 33)
• Consequence: TF NM_001354703.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• 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, 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001354703.2	c.-89-3984G>A		intron_variant	Intron 7 of 22		NP_001341632.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000291042	ENST00000460564.5	n.382-9167G>A		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50464 AN: 151994 Hom.: 8612 Cov.: 33

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.332 AC: 50503 AN: 152112 Hom.: 8622 Cov.: 33 AF XY: 0.333 AC XY: 24772 AN XY: 74352

African (AFR) AF: 0.348 AC: 14428 AN: 41516

American (AMR) AF: 0.364 AC: 5564 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 844 AN: 3470

East Asian (EAS) AF: 0.414 AC: 2140 AN: 5172

South Asian (SAS) AF: 0.397 AC: 1916 AN: 4824

European-Finnish (FIN) AF: 0.306 AC: 3240 AN: 10574

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21435 AN: 67952

Other (OTH) AF: 0.306 AC: 646 AN: 2114

Alfa AF: 0.317 Hom.: 10232

Bravo AF: 0.337

Asia WGS AF: 0.426 AC: 1480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.50
PhyloP100		-0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8177178; hg19: chr3-133463272; COSMIC: COSV53918742;