ENST00000462107.1:c.-258+18T>G

Variant names:

• chr7-100642673-A-C
• rs2075672
• ENST00000462107.1:c.-258+18T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000462107.1(TFR2):​c.-258+18T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 27)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TFR2 ENST00000462107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 43 publications found

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]

TFR2 Gene-Disease associations (from GenCC):

• hemochromatosis type 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFR2	ENST00000462107.1	c.-258+18T>G		intron_variant	Intron 1 of 18	5		ENSP00000420525.1
TFR2	ENST00000474947.1	n.89+18T>G		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 3422 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 1894

African (AFR) AF: 0.00 AC: 0 AN: 92

American (AMR) AF: 0.00 AC: 0 AN: 56

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 84

East Asian (EAS) AF: 0.00 AC: 0 AN: 228

South Asian (SAS) AF: 0.00 AC: 0 AN: 32

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 28

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2280

Other (OTH) AF: 0.00 AC: 0 AN: 210

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		1.1
PromoterAI		-0.042	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2075672; hg19: chr7-100240296;