rs3817672

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001128148.3(TFRC):c.424G>A(p.Gly142Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 1,611,674 control chromosomes in the GnomAD database, including 220,542 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.42 ( 15436 hom., cov: 31)

Exomes 𝑓: 0.52 ( 205106 hom. )

Consequence

TFRC
NM_001128148.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.01

Variant links:

Genes affected

TFRC (HGNC:11763): (transferrin receptor) This gene encodes a cell surface receptor necessary for cellular iron uptake by the process of receptor-mediated endocytosis. This receptor is required for erythropoiesis and neurologic development. Multiple alternatively spliced variants have been identified. [provided by RefSeq, Sep 2015]

TFRC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.010613E-5).

BP6

Variant 3-196073940-C-T is Benign according to our data. Variant chr3-196073940-C-T is described in ClinVar as [Benign]. Clinvar id is 1164902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFRC	NM_001128148.3 link	c.424G>A	p.Gly142Ser	missense_variant	Exon 4 of 19	ENST00000360110.9	NP_001121620.1	P02786Q7Z3E0
TFRC	NM_003234.4 link	c.424G>A	p.Gly142Ser	missense_variant	Exon 4 of 19		NP_003225.2	P02786A8K6Q8Q7Z3E0
TFRC	NM_001313965.2 link	c.181G>A	p.Gly61Ser	missense_variant	Exon 3 of 18		NP_001300894.1	P02786G3V0E5Q7Z3E0
TFRC	NM_001313966.2 link	c.-412-1788G>A		intron_variant	Intron 2 of 16		NP_001300895.1	P02786A0A8V8TM46B7Z2I6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFRC	ENST00000360110.9 link	c.424G>A	p.Gly142Ser	missense_variant	Exon 4 of 19	1	NM_001128148.3	ENSP00000353224.4		P02786

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64547

AN:

151876

Hom.:

15433

Cov.:

show subpopulations

Gnomad AFR

AF:

0.228

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.473

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.403

Gnomad FIN

AF:

0.523

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.552

Gnomad OTH

AF:

0.466

GnomAD3 exomes

AF:

0.449

AC:

112205

AN:

249668

Hom.:

27642

AF XY:

0.458

AC XY:

61748

AN XY:

134948

show subpopulations

Gnomad AFR exome

AF:

0.220

Gnomad AMR exome

AF:

0.351

Gnomad ASJ exome

AF:

0.472

Gnomad EAS exome

AF:

0.144

Gnomad SAS exome

AF:

0.414

Gnomad FIN exome

AF:

0.522

Gnomad NFE exome

AF:

0.553

Gnomad OTH exome

AF:

0.490

GnomAD4 exome

AF:

0.522

AC:

761562

AN:

1459680

Hom.:

205106

Cov.:

AF XY:

0.520

AC XY:

377245

AN XY:

726008

show subpopulations

Gnomad4 AFR exome

AF:

0.215

Gnomad4 AMR exome

AF:

0.359

Gnomad4 ASJ exome

AF:

0.471

Gnomad4 EAS exome

AF:

0.183

Gnomad4 SAS exome

AF:

0.418

Gnomad4 FIN exome

AF:

0.515

Gnomad4 NFE exome

AF:

0.560

Gnomad4 OTH exome

AF:

0.501

GnomAD4 genome

AF:

0.425

AC:

64554

AN:

151994

Hom.:

15436

Cov.:

AF XY:

0.421

AC XY:

31284

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.228

Gnomad4 AMR

AF:

0.410

Gnomad4 ASJ

AF:

0.473

Gnomad4 EAS

AF:

0.156

Gnomad4 SAS

AF:

0.404

Gnomad4 FIN

AF:

0.523

Gnomad4 NFE

AF:

0.552

Gnomad4 OTH

AF:

0.461

Alfa

AF:

0.517

Hom.:

51694

Bravo

AF:

0.405

TwinsUK

AF:

0.563

AC:

2086

ALSPAC

AF:

0.560

AC:

2159

ESP6500AA

AF:

0.228

AC:

1004

ESP6500EA

AF:

0.546

AC:

4692

ExAC

AF:

0.445

AC:

54070

Asia WGS

AF:

0.309

AC:

1075

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

TFRC-related combined immunodeficiency

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 59% of patients studied by a panel of primary immunodeficiencies. Number of patients: 57. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.0

DANN

Benign

0.82

DEOGEN2

Benign

0.0016

T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.096

T;.;T

MetaRNN

Benign

0.000050

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.6

.;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

1.1

N;N;N

REVEL

Benign

0.022

Sift

Benign

0.58

T;T;T

Sift4G

Benign

0.84

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.020

MPC

0.16

ClinPred

0.0037

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.015

gMVP

0.34

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