rs3811647

Positions:

• chr3-133765185-G-A
• chr3-133765185-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001063.4(TF):​c.1330+278G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 151,970 control chromosomes in the GnomAD database, including 7,779 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 0.31 (7779 hom., cov: 32)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.490

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TF	NM_001063.4	c.1330+278G>A		intron_variant		ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.1198+278G>A		intron_variant			NP_001341632.2
TF	NM_001354704.2	c.949+278G>A		intron_variant			NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.1330+278G>A		intron_variant		1	NM_001063.4	ENSP00000385834	P1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47170 AN: 151852 Hom.: 7767 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.311 AC: 47216 AN: 151970 Hom.: 7779 Cov.: 32 AF XY: 0.312 AC XY: 23155 AN XY: 74258

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.314

Alfa AF: 0.333 Hom.: 18419

Bravo AF: 0.313

Asia WGS AF: 0.397 AC: 1380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.44
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs3811647; hg19: chr3-133484029; COSMIC: COSV53918925; COSMIC: COSV53918925;