3-133731527-T-G

Variant names:

• chr3-133731527-T-G
• rs6439434
• NM_001354703.2:c.-89-16885T>G

Variant summary

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

The NM_001354703.2(TF):​c.-89-16885T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 151,980 control chromosomes in the GnomAD database, including 26,700 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 0.59 (26700 hom., cov: 31)
• Consequence: TF NM_001354703.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.734
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001354703.2	c.-89-16885T>G		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.382-22068T>G		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89094 AN: 151862 Hom.: 26661 Cov.: 31

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.587 AC: 89188 AN: 151980 Hom.: 26700 Cov.: 31 AF XY: 0.588 AC XY: 43700 AN XY: 74260

African (AFR) AF: 0.657 AC: 27229 AN: 41458

American (AMR) AF: 0.639 AC: 9767 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1775 AN: 3470

East Asian (EAS) AF: 0.759 AC: 3919 AN: 5166

South Asian (SAS) AF: 0.715 AC: 3436 AN: 4806

European-Finnish (FIN) AF: 0.503 AC: 5306 AN: 10544

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36116 AN: 67946

Other (OTH) AF: 0.557 AC: 1175 AN: 2110

Alfa AF: 0.549 Hom.: 69033

Bravo AF: 0.599

Asia WGS AF: 0.760 AC: 2643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.3
DANN	Benign	0.70
PhyloP100		0.73

Splicing

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

Other links and lift over

dbSNP: rs6439434; hg19: chr3-133450371;