chr3-133680858-C-T

Variant names:

• chr3-133680858-C-T
• rs2718812
• NM_001354703.2:c.-1112-7334C>T

Variant summary

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

The NM_001354703.2(TF):​c.-1112-7334C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,922 control chromosomes in the GnomAD database, including 22,144 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 0.53 (22144 hom., cov: 31)
• Consequence: TF NM_001354703.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• Publications: 15 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354703.2. 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_001354703.2		c.-1112-7334C>T		intron	N/A	NP_001341632.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000291042	ENST00000460564.5	TSL:4	n.37-7334C>T		intron	N/A
	ENSG00000291042	ENST00000490470.5	TSL:4	n.37-7334C>T		intron	N/A
	ENSG00000291042	ENST00000497521.5	TSL:4	n.36-7334C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80267 AN: 151804 Hom.: 22103 Cov.: 31

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.529 AC: 80370 AN: 151922 Hom.: 22144 Cov.: 31 AF XY: 0.530 AC XY: 39349 AN XY: 74240

African (AFR) AF: 0.691 AC: 28615 AN: 41436

American (AMR) AF: 0.509 AC: 7762 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1500 AN: 3468

East Asian (EAS) AF: 0.488 AC: 2524 AN: 5168

South Asian (SAS) AF: 0.429 AC: 2063 AN: 4812

European-Finnish (FIN) AF: 0.522 AC: 5493 AN: 10528

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30926 AN: 67946

Other (OTH) AF: 0.503 AC: 1061 AN: 2110

Alfa AF: 0.476 Hom.: 61727

Bravo AF: 0.537

Asia WGS AF: 0.515 AC: 1793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.1
DANN	Benign	0.30
PhyloP100		-0.046

Splicing

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

Other links and lift over

dbSNP: rs2718812; hg19: chr3-133399702;