3-133768777-C-G

Variant names:

• chr3-133768777-C-G
• rs1358022
• NM_001063.4:c.1622+613C>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.1622+613C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 146,002 control chromosomes in the GnomAD database, including 5,077 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 0.26 (5077 hom., cov: 28)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327
• 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, MODERATE, SUPPORTIVE, LIMITED Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001063.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	NM_001063.4	MANE Select	c.1622+613C>G		intron	N/A	NP_001054.2	P02787
	TF	NM_001354703.2		c.1490+613C>G		intron	N/A	NP_001341632.2
	TF	NM_001354704.2		c.1241+613C>G		intron	N/A	NP_001341633.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	ENST00000402696.9	TSL:1 MANE Select	c.1622+613C>G		intron	N/A	ENSP00000385834.3	P02787
	TF	ENST00000877249.1		c.974+613C>G		intron	N/A	ENSP00000547308.1
	TF	ENST00000877246.1		c.635+613C>G		intron	N/A	ENSP00000547305.1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 37231 AN: 145938 Hom.: 5076 Cov.: 28

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0660

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.284

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.255 AC: 37235 AN: 146002 Hom.: 5077 Cov.: 28 AF XY: 0.250 AC XY: 17587 AN XY: 70368

African (AFR) AF: 0.306 AC: 12007 AN: 39240

American (AMR) AF: 0.184 AC: 2625 AN: 14284

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 805 AN: 3440

East Asian (EAS) AF: 0.0662 AC: 331 AN: 4998

South Asian (SAS) AF: 0.141 AC: 663 AN: 4686

European-Finnish (FIN) AF: 0.299 AC: 2601 AN: 8686

Middle Eastern (MID) AF: 0.277 AC: 78 AN: 282

European-Non Finnish (NFE) AF: 0.256 AC: 17251 AN: 67442

Other (OTH) AF: 0.251 AC: 512 AN: 2040

Alfa AF: 0.243 Hom.: 652

Bravo AF: 0.252

Asia WGS AF: 0.132 AC: 461 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.1
DANN	Benign	0.73
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: rs1358022; hg19: chr3-133487621;