3-133746376-G-A

Variant names:

• chr3-133746376-G-A
• rs41298275
• NM_001354703.2:c.-89-2036G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001354703.2(TF):​c.-89-2036G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,389,556 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TF NM_001354703.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 0 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, MODERATE, SUPPORTIVE, LIMITED Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Genomics England PanelApp

ENSG00000291042 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	NM_001354703.2		c.-89-2036G>A		intron	N/A	NP_001341632.2
	TF	NM_001063.4	MANE Select	c.-65G>A		upstream_gene	N/A	NP_001054.2	P02787
	TF	NM_001354704.2		c.-273G>A		upstream_gene	N/A	NP_001341633.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	ENST00000466911.5	TSL:4	c.-90+127G>A		intron	N/A	ENSP00000417468.1	C9JB55
	TF	ENST00000474287.5	TSL:2	n.49G>A		non_coding_transcript_exon	Exon 1 of 3
	ENSG00000291042	ENST00000460564.5	TSL:4	n.382-7219G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1389556 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 687760

African (AFR) AF: 0.00 AC: 0 AN: 31606

American (AMR) AF: 0.00 AC: 0 AN: 36806

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25228

East Asian (EAS) AF: 0.00 AC: 0 AN: 36082

South Asian (SAS) AF: 0.00 AC: 0 AN: 79516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5560

European-Non Finnish (NFE) AF: 9.31e-7 AC: 1 AN: 1073612

Other (OTH) AF: 0.00 AC: 0 AN: 57942

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.24
DANN	Benign	0.85
PhyloP100		-1.4
PromoterAI		0.039	Neutral

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: rs41298275; hg19: chr3-133465220;