rs8177203

Positions:

• chr3-133751181-A-G

Variant summary

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

The NM_001063.4(TF):​c.217-2414A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.069 in 152,052 control chromosomes in the GnomAD database, including 498 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 0.069 (498 hom., cov: 32)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TF	NM_001063.4	c.217-2414A>G		intron_variant		ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.85-2414A>G		intron_variant			NP_001341632.2
TF	NM_001354704.2	c.-165-2414A>G		intron_variant			NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.217-2414A>G		intron_variant		1	NM_001063.4	ENSP00000385834	P1
	ENST00000460564.5	n.382-2414A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0690 AC: 10489 AN: 151936 Hom.: 496 Cov.: 32

Gnomad AFR AF: 0.0726

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0221

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0496

Gnomad OTH AF: 0.0757

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

GnomAD4 genome AF: 0.0690 AC: 10493 AN: 152052 Hom.: 498 Cov.: 32 AF XY: 0.0705 AC XY: 5239 AN XY: 74334

Gnomad4 AFR AF: 0.0726

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0599

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.0221

Gnomad4 NFE AF: 0.0496

Gnomad4 OTH AF: 0.0773

Alfa AF: 0.0575 Hom.: 75

Bravo AF: 0.0777

Asia WGS AF: 0.183 AC: 634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.82

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: rs8177203; hg19: chr3-133470025;