chr3-133765868-G-A

Variant names:

• chr3-133765868-G-A
• rs1525892
• NM_001063.4:c.1331-410G>A

Variant summary

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

The NM_001063.4(TF):​c.1331-410G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 149,070 control chromosomes in the GnomAD database, including 7,951 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 0.32 (7951 hom., cov: 32)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.540
• Publications: 18 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

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 (SAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4	c.1331-410G>A		intron_variant	Intron 11 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.1199-410G>A		intron_variant	Intron 17 of 22		NP_001341632.2
TF	NM_001354704.2	c.950-410G>A		intron_variant	Intron 10 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.1331-410G>A		intron_variant	Intron 11 of 16	1	NM_001063.4	ENSP00000385834.3

Frequencies

GnomAD3 genomes AF: 0.321 AC: 47885 AN: 148962 Hom.: 7943 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.322 AC: 47927 AN: 149070 Hom.: 7951 Cov.: 32 AF XY: 0.322 AC XY: 23470 AN XY: 72876

African (AFR) AF: 0.255 AC: 9865 AN: 38656

American (AMR) AF: 0.392 AC: 5949 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 988 AN: 3470

East Asian (EAS) AF: 0.421 AC: 2178 AN: 5170

South Asian (SAS) AF: 0.423 AC: 2033 AN: 4810

European-Finnish (FIN) AF: 0.287 AC: 3033 AN: 10568

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22853 AN: 67934

Other (OTH) AF: 0.322 AC: 669 AN: 2078

Alfa AF: 0.249 Hom.: 1096

Bravo AF: 0.319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.32
PhyloP100		0.54
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1525892; hg19: chr3-133484712;