7-100638970-T-C

Position:

• chr7-100638970-T-C

Variant summary

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

The NM_003227.4(TFR2):​c.473+1716A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 152,072 control chromosomes in the GnomAD database, including 57,856 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 0.87 (57856 hom., cov: 30)
• Consequence: TFR2 NM_003227.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFR2	NM_003227.4	c.473+1716A>G		intron_variant		ENST00000223051.8	NP_003218.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFR2	ENST00000223051.8	c.473+1716A>G		intron_variant		1	NM_003227.4	ENSP00000223051	P1
TFR2	ENST00000431692.5	c.473+1716A>G		intron_variant		5		ENSP00000413905
TFR2	ENST00000462107.1	c.473+1716A>G		intron_variant		5		ENSP00000420525	P1
TFR2	ENST00000465294.5	n.478+1716A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132230 AN: 151954 Hom.: 57802 Cov.: 30

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.866

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

GnomAD4 genome AF: 0.870 AC: 132343 AN: 152072 Hom.: 57856 Cov.: 30 AF XY: 0.868 AC XY: 64468 AN XY: 74310

Gnomad4 AFR AF: 0.948

Gnomad4 AMR AF: 0.900

Gnomad4 ASJ AF: 0.883

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.760

Gnomad4 FIN AF: 0.785

Gnomad4 NFE AF: 0.835

Gnomad4 OTH AF: 0.866

Alfa AF: 0.845 Hom.: 72985

Bravo AF: 0.885

Asia WGS AF: 0.831 AC: 2894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.59
DANN	Benign	0.63

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: rs4727457; hg19: chr7-100236593;