3-133758857-T-G

Variant names:

• chr3-133758857-T-G
• rs8177240
• NM_001063.4:c.1049-318T>G

Variant summary

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

The NM_001063.4(TF):​c.1049-318T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 151,864 control chromosomes in the GnomAD database, including 7,473 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 0.30 (7473 hom., cov: 32)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.939
• Publications: 32 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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4	c.1049-318T>G		intron_variant	Intron 8 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.917-318T>G		intron_variant	Intron 14 of 22		NP_001341632.2
TF	NM_001354704.2	c.668-318T>G		intron_variant	Intron 7 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.1049-318T>G		intron_variant	Intron 8 of 16	1	NM_001063.4	ENSP00000385834.3
TF	ENST00000485977.1	n.*105-318T>G		intron_variant	Intron 4 of 4	3		ENSP00000418716.1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45261 AN: 151748 Hom.: 7468 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.298 AC: 45298 AN: 151864 Hom.: 7473 Cov.: 32 AF XY: 0.301 AC XY: 22294 AN XY: 74184

African (AFR) AF: 0.168 AC: 6946 AN: 41398

American (AMR) AF: 0.382 AC: 5832 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1008 AN: 3466

East Asian (EAS) AF: 0.426 AC: 2204 AN: 5168

South Asian (SAS) AF: 0.425 AC: 2036 AN: 4794

European-Finnish (FIN) AF: 0.292 AC: 3067 AN: 10520

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23197 AN: 67946

Other (OTH) AF: 0.310 AC: 652 AN: 2102

Alfa AF: 0.324 Hom.: 12423

Bravo AF: 0.298

Asia WGS AF: 0.396 AC: 1377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.68
DANN	Benign	0.89
PhyloP100		-0.94
Mutation Taster		=99/1	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: rs8177240; hg19: chr3-133477701;