rs8177215

Positions:

• chr3-133754114-G-A
• chr3-133754114-G-C

Variant summary

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

The NM_001063.4(TF):​c.326-381G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0654 in 414,672 control chromosomes in the GnomAD database, including 1,444 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 0.059 (404 hom., cov: 32)
  • Exomes 𝑓: 0.069 (1040 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443

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]

ENSG00000291042 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TF	NM_001063.4	c.326-381G>A		intron_variant		ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.194-381G>A		intron_variant			NP_001341632.2
TF	NM_001354704.2	c.-56-381G>A		intron_variant			NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.326-381G>A		intron_variant		1	NM_001063.4	ENSP00000385834.3

Frequencies

GnomAD3 genomes AF: 0.0589 AC: 8963 AN: 152098 Hom.: 402 Cov.: 32

Gnomad AFR AF: 0.0386

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0996

Gnomad ASJ AF: 0.0570

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0210

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0495

Gnomad OTH AF: 0.0670

GnomAD4 exome AF: 0.0693 AC: 18175 AN: 262452 Hom.: 1040 Cov.: 0 AF XY: 0.0728 AC XY: 10228 AN XY: 140554

Gnomad4 AFR exome AF: 0.0376

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.0626

Gnomad4 EAS exome AF: 0.236

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.0220

Gnomad4 NFE exome AF: 0.0489

Gnomad4 OTH exome AF: 0.0716

GnomAD4 genome AF: 0.0589 AC: 8964 AN: 152220 Hom.: 404 Cov.: 32 AF XY: 0.0607 AC XY: 4518 AN XY: 74444

Gnomad4 AFR AF: 0.0386

Gnomad4 AMR AF: 0.0994

Gnomad4 ASJ AF: 0.0570

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.0210

Gnomad4 NFE AF: 0.0496

Gnomad4 OTH AF: 0.0691

Alfa AF: 0.0565 Hom.: 73

Bravo AF: 0.0656

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.0
DANN	Benign	0.73

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: rs8177215; hg19: chr3-133472958;