7-100627408-G-A

Position:

chr7-100627408-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003227.4(TFR2):c.1851C>T(p.Ala617Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,568,136 control chromosomes in the GnomAD database, including 29,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2223 hom., cov: 33)

Exomes 𝑓: 0.19 ( 26810 hom. )

Consequence

TFR2
NM_003227.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: -1.56

Variant links:

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 links:

LOC124901709 (HGNC:):

LOC124901709 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 7-100627408-G-A is Benign according to our data. Variant chr7-100627408-G-A is described in ClinVar as [Benign]. Clinvar id is 21369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-100627408-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.56 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFR2	NM_003227.4 link	c.1851C>T	p.Ala617Ala	synonymous_variant	16/18	ENST00000223051.8	NP_003218.2	Q9UP52-1
TFR2	NM_001206855.3 link	c.1338C>T	p.Ala446Ala	synonymous_variant	13/15		NP_001193784.1	Q9UP52-2
LOC124901709	XR_007060454.1 link	n.434-3748G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFR2	ENST00000223051.8 link	c.1851C>T	p.Ala617Ala	synonymous_variant	16/18	1	NM_003227.4	ENSP00000223051.3		Q9UP52-1

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

24633

AN:

152140

Hom.:

2220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0889

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.185

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.156

GnomAD3 exomes

AF:

0.176

AC:

31394

AN:

178406

Hom.:

2983

AF XY:

0.176

AC XY:

16705

AN XY:

94862

show subpopulations

Gnomad AFR exome

AF:

0.0901

Gnomad AMR exome

AF:

0.165

Gnomad ASJ exome

AF:

0.188

Gnomad EAS exome

AF:

0.121

Gnomad SAS exome

AF:

0.131

Gnomad FIN exome

AF:

0.218

Gnomad NFE exome

AF:

0.206

Gnomad OTH exome

AF:

0.175

GnomAD4 exome

AF:

0.191

AC:

269930

AN:

1415878

Hom.:

26810

Cov.:

AF XY:

0.190

AC XY:

132885

AN XY:

700108

show subpopulations

Gnomad4 AFR exome

AF:

0.0815

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.185

Gnomad4 EAS exome

AF:

0.112

Gnomad4 SAS exome

AF:

0.135

Gnomad4 FIN exome

AF:

0.214

Gnomad4 NFE exome

AF:

0.201

Gnomad4 OTH exome

AF:

0.182

GnomAD4 genome

AF:

0.162

AC:

24645

AN:

152258

Hom.:

2223

Cov.:

AF XY:

0.159

AC XY:

11862

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0890

Gnomad4 AMR

AF:

0.153

Gnomad4 ASJ

AF:

0.185

Gnomad4 EAS

AF:

0.120

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.221

Gnomad4 NFE

AF:

0.204

Gnomad4 OTH

AF:

0.154

Alfa

AF:

0.189

Hom.:

3259

Bravo

AF:

0.155

Asia WGS

AF:

0.128

AC:

445

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hemochromatosis type 3

Benign:2Other:1

not provided, no classification provided	literature only	GeneReviews	-	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Aug 15, 2023	- -

Hereditary hemochromatosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Hereditary hemochromatosis type 4

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

1.9

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over