rs2239641

Positions:

• chr3-196062543-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.500

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]

ACMG classification

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/exons	MANE	UniProt
TFRC	NM_001128148.3	c.1468+39A>G		intron_variant		ENST00000360110.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFRC	ENST00000360110.9	c.1468+39A>G		intron_variant		1	NM_001128148.3	P2

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73313 AN: 152050 Hom.: 19441 Cov.: 33

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

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.: 24 AF XY: 0.578 AC XY: 410071 AN XY: 709408

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.: 33 AF XY: 0.478 AC XY: 35541 AN XY: 74386

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

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

Other links and lift over

dbSNP: rs2239641; hg19: chr3-195789414; COSMIC: COSV64054884; COSMIC: COSV64054884;