rs2715631

Positions:

• chr3-133764045-T-G

Variant summary

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

The ENST00000402696.9(TF):​c.1204-137T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 744,354 control chromosomes in the GnomAD database, including 19,345 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 0.20 (3506 hom., cov: 33)
  • Exomes 𝑓: 0.22 (15839 hom.)
• Consequence: TF ENST00000402696.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TF	NM_001063.4	c.1204-137T>G		intron_variant		ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.1072-137T>G		intron_variant			NP_001341632.2
TF	NM_001354704.2	c.823-137T>G		intron_variant			NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.1204-137T>G		intron_variant		1	NM_001063.4	ENSP00000385834	P1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30387 AN: 152104 Hom.: 3505 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0677

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.221 AC: 130579 AN: 592132 Hom.: 15839 AF XY: 0.218 AC XY: 69907 AN XY: 320978

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.129

Gnomad4 ASJ exome AF: 0.234

Gnomad4 EAS exome AF: 0.0811

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.307

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.225

GnomAD4 genome AF: 0.199 AC: 30368 AN: 152222 Hom.: 3506 Cov.: 33 AF XY: 0.199 AC XY: 14798 AN XY: 74410

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.0678

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.210

Alfa AF: 0.218 Hom.: 1039

Bravo AF: 0.185

Asia WGS AF: 0.124 AC: 430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.087
DANN	Benign	0.72

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: rs2715631; hg19: chr3-133482889;