rs7385804

Variant names:

• chr7-100638347-C-A
• rs7385804
• NM_003227.4:c.473+2339G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-100638347-C-A
• chr7-100638347-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003227.4(TFR2):​c.473+2339G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 151,638 control chromosomes in the GnomAD database, including 32,338 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 (32338 hom., cov: 29)
• Consequence: TFR2 NM_003227.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.14
• Publications: 91 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFR2	NM_003227.4	c.473+2339G>T		intron_variant	Intron 3 of 17	ENST00000223051.8	NP_003218.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFR2	ENST00000223051.8	c.473+2339G>T		intron_variant	Intron 3 of 17	1	NM_003227.4	ENSP00000223051.3
TFR2	ENST00000462107.1	c.473+2339G>T		intron_variant	Intron 4 of 18	5		ENSP00000420525.1
TFR2	ENST00000431692.5	c.473+2339G>T		intron_variant	Intron 3 of 15	5		ENSP00000413905.1
TFR2	ENST00000465294.5	n.478+2339G>T		intron_variant	Intron 3 of 13	2

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98501 AN: 151520 Hom.: 32318 Cov.: 29

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.650 AC: 98571 AN: 151638 Hom.: 32338 Cov.: 29 AF XY: 0.652 AC XY: 48319 AN XY: 74074

African (AFR) AF: 0.680 AC: 28113 AN: 41346

American (AMR) AF: 0.728 AC: 11089 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2416 AN: 3462

East Asian (EAS) AF: 0.782 AC: 4011 AN: 5128

South Asian (SAS) AF: 0.633 AC: 3026 AN: 4782

European-Finnish (FIN) AF: 0.536 AC: 5626 AN: 10500

Middle Eastern (MID) AF: 0.747 AC: 218 AN: 292

European-Non Finnish (NFE) AF: 0.621 AC: 42198 AN: 67904

Other (OTH) AF: 0.673 AC: 1413 AN: 2100

Alfa AF: 0.637 Hom.: 96665

Bravo AF: 0.666

Asia WGS AF: 0.687 AC: 2393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.37
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs7385804; hg19: chr7-100235970;