3-133751011-G-C

Position:

• chr3-133751011-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.216+2427G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,026 control chromosomes in the GnomAD database, including 873 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 0.10 (873 hom., cov: 32)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TF	NM_001063.4	c.216+2427G>C		intron_variant		ENST00000402696.9
TF	NM_001354703.2	c.84+2427G>C		intron_variant
TF	NM_001354704.2	c.-165-2584G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TF	ENST00000402696.9	c.216+2427G>C		intron_variant		1	NM_001063.4	P1
	ENST00000460564.5	n.382-2584G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15719 AN: 151912 Hom.: 872 Cov.: 32

Gnomad AFR AF: 0.0828

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0318

Gnomad SAS AF: 0.0846

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.0946

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

GnomAD4 genome AF: 0.104 AC: 15738 AN: 152026 Hom.: 873 Cov.: 32 AF XY: 0.103 AC XY: 7663 AN XY: 74286

Gnomad4 AFR AF: 0.0828

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.0318

Gnomad4 SAS AF: 0.0847

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.0978

Alfa AF: 0.0553 Hom.: 61

Bravo AF: 0.101

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.8
DANN	Benign	0.52

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: rs8177201; hg19: chr3-133469855;