dbSNP rs2239641: TFRC:c.1468+39A>G (chr3-196062543-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.1468+39A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 1,574,680 control chromosomes in the GnomAD database, including 264,268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 19438 hom., cov: 33)

Exomes 𝑓: 0.58 ( 244830 hom. )

Consequence

TFRC
NM_001128148.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.500

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=-0.8).

BP6

Variant 3-196062543-T-C is Benign according to our data. Variant chr3-196062543-T-C is described in ClinVar as [Benign]. Clinvar id is 1273355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFRC	NM_001128148.3 link	c.1468+39A>G		intron_variant	Intron 13 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.1468+39A>G		intron_variant	Intron 13 of 18	1	NM_001128148.3	ENSP00000353224.4		P02786

Frequencies

GnomAD3 genomes

AF:

0.482

AC:

73313

AN:

152050

Hom.:

19441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.294

Gnomad AMI

AF:

0.386

Gnomad AMR

AF:

0.450

Gnomad ASJ

AF:

0.557

Gnomad EAS

AF:

0.167

Gnomad SAS

AF:

0.512

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.608

Gnomad OTH

AF:

0.521

GnomAD3 exomes

AF:

0.503

AC:

119475

AN:

237402

Hom.:

32722

AF XY:

0.515

AC XY:

66380

AN XY:

128920

show subpopulations

Gnomad AFR exome

AF:

0.282

Gnomad AMR exome

AF:

0.370

Gnomad ASJ exome

AF:

0.548

Gnomad EAS exome

AF:

0.153

Gnomad SAS exome

AF:

0.518

Gnomad FIN exome

AF:

0.566

Gnomad NFE exome

AF:

0.606

Gnomad OTH exome

AF:

0.545

GnomAD4 exome

AF:

0.578

AC:

822548

AN:

1422512

Hom.:

244830

Cov.:

AF XY:

0.578

AC XY:

410071

AN XY:

709408

show subpopulations

Gnomad4 AFR exome

AF:

0.283

Gnomad4 AMR exome

AF:

0.380

Gnomad4 ASJ exome

AF:

0.546

Gnomad4 EAS exome

AF:

0.200

Gnomad4 SAS exome

AF:

0.527

Gnomad4 FIN exome

AF:

0.560

Gnomad4 NFE exome

AF:

0.614

Gnomad4 OTH exome

AF:

0.558

GnomAD4 genome

AF:

0.482

AC:

73322

AN:

152168

Hom.:

19438

Cov.:

AF XY:

0.478

AC XY:

35541

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.294

Gnomad4 AMR

AF:

0.449

Gnomad4 ASJ

AF:

0.557

Gnomad4 EAS

AF:

0.166

Gnomad4 SAS

AF:

0.514

Gnomad4 FIN

AF:

0.569

Gnomad4 NFE

AF:

0.608

Gnomad4 OTH

AF:

0.515

Alfa

AF:

0.553

Hom.:

4514

Bravo

AF:

0.460

Asia WGS

AF:

0.363

AC:

1265

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

Jun 19, 2021

GeneDx

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

- -

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 65% of patients studied by a panel of primary immunodeficiencies. Number of patients: 62. Only high quality variants are reported. -

TFRC-related combined immunodeficiency

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.1

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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