rs4434553

Positions:

• chr7-100642568-A-G

Variant summary

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

The ENST00000462107.1(TFR2):​c.-258+123T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 151,980 control chromosomes in the GnomAD database, including 12,680 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 0.39 (12632 hom., cov: 29)
  • Exomes 𝑓: 0.46 (48 hom.)
• Consequence: TFR2 ENST00000462107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.682

Genes affected

TFR2 (HGNC:11762): (transferrin receptor 2) This gene encodes a single-pass type II membrane protein, which is a member of the transferrin receptor-like family. This protein mediates cellular uptake of transferrin-bound iron, and may be involved in iron metabolism, hepatocyte function and erythrocyte differentiation. Mutations in this gene have been associated with hereditary hemochromatosis type III. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, May 2011]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.100642568A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFR2	ENST00000462107.1	c.-258+123T>C		intron_variant		5		ENSP00000420525.1
TFR2	ENST00000474947.1	n.89+123T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59485 AN: 151462 Hom.: 12635 Cov.: 29

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.423

GnomAD4 exome AF: 0.455 AC: 183 AN: 402 Hom.: 48 AF XY: 0.462 AC XY: 110 AN XY: 238

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.0500

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.354

Gnomad4 NFE exome AF: 0.504

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.392 AC: 59489 AN: 151578 Hom.: 12632 Cov.: 29 AF XY: 0.386 AC XY: 28613 AN XY: 74032

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.419

Alfa AF: 0.470 Hom.: 22092

Bravo AF: 0.386

Asia WGS AF: 0.219 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.32

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4434553; hg19: chr7-100240191;