rs8177235

Variant names:

• chr3-133757239-G-A
• rs8177235
• NM_001063.4:c.870+230G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001063.4(TF):​c.870+230G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0757 in 152,232 control chromosomes in the GnomAD database, including 562 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 0.076 (562 hom., cov: 32)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 7 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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4	c.870+230G>A		intron_variant	Intron 7 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.738+230G>A		intron_variant	Intron 13 of 22		NP_001341632.2
TF	NM_001354704.2	c.489+230G>A		intron_variant	Intron 6 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.870+230G>A		intron_variant	Intron 7 of 16	1	NM_001063.4	ENSP00000385834.3
TF	ENST00000485977.1	n.235+230G>A		intron_variant	Intron 3 of 4	3		ENSP00000418716.1

Frequencies

GnomAD3 genomes AF: 0.0757 AC: 11519 AN: 152114 Hom.: 559 Cov.: 32

Gnomad AFR AF: 0.0640

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0590

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0796

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0615

Gnomad OTH AF: 0.0817

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

GnomAD4 genome AF: 0.0757 AC: 11527 AN: 152232 Hom.: 562 Cov.: 32 AF XY: 0.0790 AC XY: 5883 AN XY: 74432

African (AFR) AF: 0.0642 AC: 2666 AN: 41554

American (AMR) AF: 0.101 AC: 1547 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0590 AC: 205 AN: 3472

East Asian (EAS) AF: 0.243 AC: 1252 AN: 5152

South Asian (SAS) AF: 0.116 AC: 559 AN: 4816

European-Finnish (FIN) AF: 0.0796 AC: 845 AN: 10610

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0615 AC: 4182 AN: 68006

Other (OTH) AF: 0.0823 AC: 174 AN: 2114

Alfa AF: 0.0692 Hom.: 731

Bravo AF: 0.0784

Asia WGS AF: 0.178 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.9
DANN	Benign	0.75
PhyloP100		0.018
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: rs8177235; hg19: chr3-133476083; COSMIC: COSV107300590; COSMIC: COSV107300590;