rs2718806

Variant names:

• chr3-133767249-G-A
• rs2718806
• NM_001063.4:c.1487-780G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-133767249-G-A
• chr3-133767249-G-T

Variant summary

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

The NM_001063.4(TF):​c.1487-780G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,958 control chromosomes in the GnomAD database, including 7,126 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 0.29 (7126 hom., cov: 32)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4	c.1487-780G>A		intron_variant	Intron 12 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.1355-780G>A		intron_variant	Intron 18 of 22		NP_001341632.2
TF	NM_001354704.2	c.1106-780G>A		intron_variant	Intron 11 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.1487-780G>A		intron_variant	Intron 12 of 16	1	NM_001063.4	ENSP00000385834.3
TF	ENST00000461695.1	n.155-780G>A		intron_variant	Intron 1 of 6	3		ENSP00000419714.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44366 AN: 151840 Hom.: 7118 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.0678

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.292 AC: 44395 AN: 151958 Hom.: 7126 Cov.: 32 AF XY: 0.287 AC XY: 21307 AN XY: 74288

African (AFR) AF: 0.407 AC: 16858 AN: 41414

American (AMR) AF: 0.209 AC: 3191 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 819 AN: 3464

East Asian (EAS) AF: 0.0679 AC: 351 AN: 5166

South Asian (SAS) AF: 0.137 AC: 657 AN: 4810

European-Finnish (FIN) AF: 0.321 AC: 3396 AN: 10564

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18086 AN: 67942

Other (OTH) AF: 0.276 AC: 583 AN: 2112

Alfa AF: 0.283 Hom.: 949

Bravo AF: 0.291

Asia WGS AF: 0.141 AC: 492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.35
PhyloP100		-0.47
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: rs2718806; hg19: chr3-133486093;