Genetic Variant TFRC:c.687+9A>G (chr3-196071387-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001128148.3(TFRC):c.687+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.954 in 1,611,512 control chromosomes in the GnomAD database, including 735,999 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.90 ( 62505 hom., cov: 32)

Exomes 𝑓: 0.96 ( 673494 hom. )

Consequence

TFRC
NM_001128148.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.545

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 (BayesDel_noAF=-0.82).

BP6

Variant 3-196071387-T-C is Benign according to our data. Variant chr3-196071387-T-C is described in ClinVar as [Benign]. Clinvar id is 1164901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFRC	NM_001128148.3 link	c.687+9A>G		intron_variant	Intron 6 of 18	ENST00000360110.9	NP_001121620.1	P02786Q7Z3E0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFRC	ENST00000360110.9 link	c.687+9A>G		intron_variant	Intron 6 of 18	1	NM_001128148.3	ENSP00000353224.4		P02786

Frequencies

GnomAD3 genomes

AF:

0.900

AC:

136866

AN:

152092

Hom.:

62465

Cov.:

show subpopulations

Gnomad AFR

AF:

0.731

Gnomad AMI

AF:

0.908

Gnomad AMR

AF:

0.944

Gnomad ASJ

AF:

0.980

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.988

Gnomad FIN

AF:

0.964

Gnomad MID

AF:

0.911

Gnomad NFE

AF:

0.964

Gnomad OTH

AF:

0.911

GnomAD3 exomes

AF:

0.954

AC:

239724

AN:

251366

Hom.:

114808

AF XY:

0.958

AC XY:

130194

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.718

Gnomad AMR exome

AF:

0.961

Gnomad ASJ exome

AF:

0.974

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.988

Gnomad FIN exome

AF:

0.971

Gnomad NFE exome

AF:

0.963

Gnomad OTH exome

AF:

0.950

GnomAD4 exome

AF:

0.960

AC:

1400750

AN:

1459302

Hom.:

673494

Cov.:

AF XY:

0.961

AC XY:

698098

AN XY:

726056

show subpopulations

Gnomad4 AFR exome

AF:

0.717

Gnomad4 AMR exome

AF:

0.958

Gnomad4 ASJ exome

AF:

0.975

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.987

Gnomad4 FIN exome

AF:

0.969

Gnomad4 NFE exome

AF:

0.964

Gnomad4 OTH exome

AF:

0.950

GnomAD4 genome

AF:

0.900

AC:

136967

AN:

152210

Hom.:

62505

Cov.:

AF XY:

0.903

AC XY:

67247

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.731

Gnomad4 AMR

AF:

0.944

Gnomad4 ASJ

AF:

0.980

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.989

Gnomad4 FIN

AF:

0.964

Gnomad4 NFE

AF:

0.964

Gnomad4 OTH

AF:

0.911

Alfa

AF:

0.942

Hom.:

82994

Bravo

AF:

0.888

Asia WGS

AF:

0.977

AC:

3398

AN:

3478

EpiCase

AF:

0.960

EpiControl

AF:

0.960

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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 100% of patients studied by a panel of primary immunodeficiencies. Number of patients: 96. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.1

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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