3-133751011-G-C

Variant names:

• chr3-133751011-G-C
• rs8177201
• NM_001063.4:c.216+2427G>C

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.95).
• 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 rank	MANE	Protein	UniProt
TF	NM_001063.4	c.216+2427G>C		intron_variant	Intron 2 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.84+2427G>C		intron_variant	Intron 8 of 22		NP_001341632.2
TF	NM_001354704.2	c.-165-2584G>C		intron_variant	Intron 1 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.216+2427G>C		intron_variant	Intron 2 of 16	1	NM_001063.4	ENSP00000385834.3

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

African (AFR) AF: 0.0828 AC: 3435 AN: 41470

American (AMR) AF: 0.113 AC: 1730 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3470

East Asian (EAS) AF: 0.0318 AC: 165 AN: 5184

South Asian (SAS) AF: 0.0847 AC: 408 AN: 4818

European-Finnish (FIN) AF: 0.114 AC: 1196 AN: 10524

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7875 AN: 67970

Other (OTH) AF: 0.0978 AC: 207 AN: 2116

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
PhyloP100		0.16
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: rs8177201; hg19: chr3-133469855;