NM_003227.4:c.473+49C>A

Variant names:

• chr7-100640637-G-T
• rs80338874
• NM_003227.4:c.473+49C>A

Variant summary

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

The NM_003227.4(TFR2):​c.473+49C>A 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. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TFR2 NM_003227.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.171
• Publications: 0 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=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003227.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFR2	NM_003227.4	MANE Select	c.473+49C>A		intron	N/A	NP_003218.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFR2	ENST00000223051.8	TSL:1 MANE Select	c.473+49C>A		intron	N/A	ENSP00000223051.3
	TFR2	ENST00000474947.1	TSL:2	n.680C>A		non_coding_transcript_exon	Exon 4 of 4
	TFR2	ENST00000462107.1	TSL:5	c.473+49C>A		intron	N/A	ENSP00000420525.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1444252 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 718094

African (AFR) AF: 0.00 AC: 0 AN: 33288

American (AMR) AF: 0.00 AC: 0 AN: 44370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25880

East Asian (EAS) AF: 0.00 AC: 0 AN: 39564

South Asian (SAS) AF: 0.00 AC: 0 AN: 85632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4792

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106184

Other (OTH) AF: 0.00 AC: 0 AN: 59804

GnomAD4 genome Cov.: 31

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Hemochromatosis type 3 Other:1

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.49
PhyloP100		-0.17

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

Other links and lift over

dbSNP: rs80338874; hg19: chr7-100238260;