7-100642673-A-G

Position:

• chr7-100642673-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+18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 154,586 control chromosomes in the GnomAD database, including 32,651 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 0.65 (31961 hom., cov: 27)
  • Exomes 𝑓: 0.62 (690 hom.)
• Consequence: TFR2 ENST00000462107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.100642673A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFR2	ENST00000462107.1	c.-258+18T>C		intron_variant		5		ENSP00000420525.1
TFR2	ENST00000474947.1	n.89+18T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.647 AC: 97795 AN: 151064 Hom.: 31945 Cov.: 27

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.669

GnomAD4 exome AF: 0.623 AC: 2121 AN: 3404 Hom.: 690 Cov.: 0 AF XY: 0.619 AC XY: 1169 AN XY: 1888

Gnomad4 AFR exome AF: 0.674

Gnomad4 AMR exome AF: 0.685

Gnomad4 ASJ exome AF: 0.607

Gnomad4 EAS exome AF: 0.846

Gnomad4 SAS exome AF: 0.656

Gnomad4 FIN exome AF: 0.512

Gnomad4 NFE exome AF: 0.606

Gnomad4 OTH exome AF: 0.724

GnomAD4 genome AF: 0.647 AC: 97851 AN: 151182 Hom.: 31961 Cov.: 27 AF XY: 0.649 AC XY: 47922 AN XY: 73806

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.729

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.671

Alfa AF: 0.641 Hom.: 54317

Bravo AF: 0.663

Asia WGS AF: 0.687 AC: 2392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.87

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2075672; hg19: chr7-100240296;