7-100628248-G-A

Position:

chr7-100628248-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003227.4(TFR2):c.1449C>T(p.Ser483Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,602,130 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0062 ( 9 hom., cov: 31)

Exomes 𝑓: 0.00059 ( 5 hom. )

Consequence

TFR2
NM_003227.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.334

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:

TFR2 (HGNC:):

TFR2 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=-0.61).

BP6

Variant 7-100628248-G-A is Benign according to our data. Variant chr7-100628248-G-A is described in ClinVar as [Benign]. Clinvar id is 258986.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.334 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00615 (900/146274) while in subpopulation AFR AF= 0.0208 (820/39462). AF 95% confidence interval is 0.0196. There are 9 homozygotes in gnomad4. There are 430 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFR2	NM_003227.4 linkuse as main transcript	c.1449C>T	p.Ser483Ser	synonymous_variant	11/18	ENST00000223051.8	NP_003218.2	Q9UP52-1
TFR2	NM_001206855.3 linkuse as main transcript	c.936C>T	p.Ser312Ser	synonymous_variant	8/15		NP_001193784.1	Q9UP52-2
LOC124901709	XR_007060454.1 linkuse as main transcript	n.434-2908G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFR2	ENST00000223051.8 linkuse as main transcript	c.1449C>T	p.Ser483Ser	synonymous_variant	11/18	1	NM_003227.4	ENSP00000223051.3		Q9UP52-1

Frequencies

GnomAD3 genomes

AF:

0.00615

AC:

899

AN:

146182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0208

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00396

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.0000894

Gnomad OTH

AF:

0.00845

GnomAD3 exomes

AF:

0.00147

AC:

369

AN:

251390

Hom.:

AF XY:

0.00102

AC XY:

138

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.0198

Gnomad AMR exome

AF:

0.000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000593

AC:

864

AN:

1455856

Hom.:

Cov.:

AF XY:

0.000507

AC XY:

367

AN XY:

724226

show subpopulations

Gnomad4 AFR exome

AF:

0.0209

Gnomad4 AMR exome

AF:

0.00117

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000307

Gnomad4 OTH exome

AF:

0.00130

GnomAD4 genome

AF:

0.00615

AC:

900

AN:

146274

Hom.:

Cov.:

AF XY:

0.00607

AC XY:

430

AN XY:

70866

show subpopulations

Gnomad4 AFR

AF:

0.0208

Gnomad4 AMR

AF:

0.00395

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000894

Gnomad4 OTH

AF:

0.00837

Alfa

AF:

0.00233

Hom.:

Bravo

AF:

0.00644

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hemochromatosis type 3

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Hereditary hemochromatosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.3

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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