chr3-133759713-T-G

Variant names:

• chr3-133759713-T-G
• rs6762415
• NM_001063.4:c.1203+384T>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.1203+384T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,868 control chromosomes in the GnomAD database, including 19,761 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 0.50 (19761 hom., cov: 31)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.659 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	NM_001063.4	MANE Select	c.1203+384T>G		intron	N/A	NP_001054.2
	TF	NM_001354703.2		c.1071+384T>G		intron	N/A	NP_001341632.2
	TF	NM_001354704.2		c.822+384T>G		intron	N/A	NP_001341633.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	ENST00000402696.9	TSL:1 MANE Select	c.1203+384T>G		intron	N/A	ENSP00000385834.3

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76486 AN: 151750 Hom.: 19740 Cov.: 31

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.504 AC: 76562 AN: 151868 Hom.: 19761 Cov.: 31 AF XY: 0.505 AC XY: 37447 AN XY: 74222

African (AFR) AF: 0.421 AC: 17428 AN: 41396

American (AMR) AF: 0.568 AC: 8674 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1794 AN: 3470

East Asian (EAS) AF: 0.678 AC: 3498 AN: 5158

South Asian (SAS) AF: 0.657 AC: 3154 AN: 4802

European-Finnish (FIN) AF: 0.412 AC: 4344 AN: 10546

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35948 AN: 67924

Other (OTH) AF: 0.526 AC: 1110 AN: 2112

Alfa AF: 0.372 Hom.: 1119

Bravo AF: 0.512

Asia WGS AF: 0.610 AC: 2122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.39
PhyloP100		-0.43
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: rs6762415; hg19: chr3-133478557; COSMIC: COSV53918834; COSMIC: COSV53918834;