3-133754781-G-T

Variant names:

• chr3-133754781-G-T
• rs8177220
• NM_001063.4:c.502+110G>T

Variant summary

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

The NM_001063.4(TF):​c.502+110G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0566 in 1,213,184 control chromosomes in the GnomAD database, including 2,583 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 0.067 (378 hom., cov: 32)
  • Exomes 𝑓: 0.055 (2205 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4	c.502+110G>T		intron_variant	Intron 4 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.370+110G>T		intron_variant	Intron 10 of 22		NP_001341632.2
TF	NM_001354704.2	c.121+110G>T		intron_variant	Intron 3 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.502+110G>T		intron_variant	Intron 4 of 16	1	NM_001063.4	ENSP00000385834.3

Frequencies

GnomAD3 genomes AF: 0.0667 AC: 10154 AN: 152174 Hom.: 372 Cov.: 32

Gnomad AFR AF: 0.0984

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0390

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.0548

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0841

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0479

Gnomad OTH AF: 0.0541

GnomAD4 exome AF: 0.0552 AC: 58509 AN: 1060892 Hom.: 2205 AF XY: 0.0583 AC XY: 31787 AN XY: 545206

African (AFR) AF: 0.101 AC: 2591 AN: 25566

American (AMR) AF: 0.0347 AC: 1519 AN: 43782

Ashkenazi Jewish (ASJ) AF: 0.0778 AC: 1841 AN: 23650

East Asian (EAS) AF: 0.0499 AC: 1884 AN: 37780

South Asian (SAS) AF: 0.133 AC: 10276 AN: 77482

European-Finnish (FIN) AF: 0.0841 AC: 4381 AN: 52084

Middle Eastern (MID) AF: 0.0804 AC: 283 AN: 3520

European-Non Finnish (NFE) AF: 0.0440 AC: 32963 AN: 749864

Other (OTH) AF: 0.0588 AC: 2771 AN: 47164

GnomAD4 genome AF: 0.0669 AC: 10186 AN: 152292 Hom.: 378 Cov.: 32 AF XY: 0.0683 AC XY: 5089 AN XY: 74472

African (AFR) AF: 0.0990 AC: 4114 AN: 41562

American (AMR) AF: 0.0389 AC: 596 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0775 AC: 269 AN: 3470

East Asian (EAS) AF: 0.0548 AC: 284 AN: 5184

South Asian (SAS) AF: 0.130 AC: 628 AN: 4822

European-Finnish (FIN) AF: 0.0841 AC: 893 AN: 10614

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0479 AC: 3258 AN: 68018

Other (OTH) AF: 0.0545 AC: 115 AN: 2110

Alfa AF: 0.0520 Hom.: 98

Bravo AF: 0.0630

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.4
DANN	Benign	0.58
PhyloP100		0.21
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: rs8177220; hg19: chr3-133473625;