rs8177203

Variant names:

• chr3-133751181-A-G
• rs8177203
• NM_001063.4:c.217-2414A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.89).
• 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 rank	MANE	Protein	UniProt
TF	NM_001063.4	c.217-2414A>G		intron_variant	Intron 2 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.85-2414A>G		intron_variant	Intron 8 of 22		NP_001341632.2
TF	NM_001354704.2	c.-165-2414A>G		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.217-2414A>G		intron_variant	Intron 2 of 16	1	NM_001063.4	ENSP00000385834.3

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

African (AFR) AF: 0.0726 AC: 3009 AN: 41432

American (AMR) AF: 0.103 AC: 1568 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 208 AN: 3472

East Asian (EAS) AF: 0.247 AC: 1274 AN: 5168

South Asian (SAS) AF: 0.116 AC: 561 AN: 4826

European-Finnish (FIN) AF: 0.0221 AC: 234 AN: 10580

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.0496 AC: 3374 AN: 67988

Other (OTH) AF: 0.0773 AC: 163 AN: 2110

Alfa AF: 0.0581 Hom.: 109

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
PhyloP100		-0.026
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: rs8177203; hg19: chr3-133470025;