3-133755159-C-G

Variant names:

• chr3-133755159-C-G
• rs8177224
• NM_001063.4:c.503-204C>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.503-204C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,148 control chromosomes in the GnomAD database, including 6,853 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 0.29 (6853 hom., cov: 33)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334
• Publications: 6 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

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 = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4	c.503-204C>G		intron_variant	Intron 4 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.371-204C>G		intron_variant	Intron 10 of 22		NP_001341632.2
TF	NM_001354704.2	c.122-204C>G		intron_variant	Intron 3 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.503-204C>G		intron_variant	Intron 4 of 16	1	NM_001063.4	ENSP00000385834.3

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43811 AN: 152030 Hom.: 6851 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.288 AC: 43835 AN: 152148 Hom.: 6853 Cov.: 33 AF XY: 0.290 AC XY: 21589 AN XY: 74366

African (AFR) AF: 0.191 AC: 7911 AN: 41522

American (AMR) AF: 0.351 AC: 5366 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 834 AN: 3470

East Asian (EAS) AF: 0.440 AC: 2271 AN: 5166

South Asian (SAS) AF: 0.406 AC: 1959 AN: 4824

European-Finnish (FIN) AF: 0.299 AC: 3160 AN: 10572

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.315 AC: 21411 AN: 67978

Other (OTH) AF: 0.281 AC: 593 AN: 2112

Alfa AF: 0.299 Hom.: 976

Bravo AF: 0.287

Asia WGS AF: 0.411 AC: 1428 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	0.40
DANN	Benign	0.59
PhyloP100		-0.33
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: rs8177224; hg19: chr3-133474003; COSMIC: COSV53918795; COSMIC: COSV53918795;