rs3811647

Variant names:

• chr3-133765185-G-A
• rs3811647
• NM_001063.4:c.1330+278G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 95 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.408 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.1330+278G>A		intron	N/A	NP_001054.2	P02787
	TF	NM_001354703.2		c.1198+278G>A		intron	N/A	NP_001341632.2
	TF	NM_001354704.2		c.949+278G>A		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.1330+278G>A		intron	N/A	ENSP00000385834.3	P02787
	TF	ENST00000877249.1		c.682+278G>A		intron	N/A	ENSP00000547308.1
	TF	ENST00000877246.1		c.343+278G>A		intron	N/A	ENSP00000547305.1

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

African (AFR) AF: 0.222 AC: 9219 AN: 41434

American (AMR) AF: 0.386 AC: 5901 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 990 AN: 3468

East Asian (EAS) AF: 0.420 AC: 2165 AN: 5160

South Asian (SAS) AF: 0.423 AC: 2034 AN: 4810

European-Finnish (FIN) AF: 0.287 AC: 3031 AN: 10558

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22856 AN: 67938

Other (OTH) AF: 0.314 AC: 664 AN: 2114

Alfa AF: 0.334 Hom.: 36872

Bravo AF: 0.313

Asia WGS AF: 0.397 AC: 1380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.44
DANN	Benign	0.41
PhyloP100		-0.49
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: rs3811647; hg19: chr3-133484029; COSMIC: COSV53918925; COSMIC: COSV53918925;