rs8177277

Positions:

• chr3-133765986-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000402696.9(TF):​c.1331-292T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0516 in 152,338 control chromosomes in the GnomAD database, including 277 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 0.052 (277 hom., cov: 33)
• Consequence: TF ENST00000402696.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TF	NM_001063.4	c.1331-292T>C		intron_variant		ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.1199-292T>C		intron_variant			NP_001341632.2
TF	NM_001354704.2	c.950-292T>C		intron_variant			NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.1331-292T>C		intron_variant		1	NM_001063.4	ENSP00000385834	P1

Frequencies

GnomAD3 genomes AF: 0.0516 AC: 7857 AN: 152220 Hom.: 278 Cov.: 33

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0677

Gnomad ASJ AF: 0.0539

Gnomad EAS AF: 0.0225

Gnomad SAS AF: 0.0221

Gnomad FIN AF: 0.0752

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0716

Gnomad OTH AF: 0.0406

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

GnomAD4 genome AF: 0.0516 AC: 7857 AN: 152338 Hom.: 277 Cov.: 33 AF XY: 0.0520 AC XY: 3875 AN XY: 74494

Gnomad4 AFR AF: 0.0142

Gnomad4 AMR AF: 0.0676

Gnomad4 ASJ AF: 0.0539

Gnomad4 EAS AF: 0.0224

Gnomad4 SAS AF: 0.0219

Gnomad4 FIN AF: 0.0752

Gnomad4 NFE AF: 0.0716

Gnomad4 OTH AF: 0.0407

Alfa AF: 0.0622 Hom.: 99

Bravo AF: 0.0492

Asia WGS AF: 0.0240 AC: 82 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.29
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs8177277; hg19: chr3-133484830;