3-196071387-T-C

Variant names:

• chr3-196071387-T-C
• rs480760
• NM_001128148.3:c.687+9A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.545
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• TFRC-related combined immunodeficiency

  Inheritance: AR, Unknown Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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	c.687+9A>G		intron_variant	Intron 6 of 18	ENST00000360110.9	NP_001121620.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.900 AC: 136866 AN: 152092 Hom.: 62465 Cov.: 32

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

GnomAD2 exomes AF: 0.954 AC: 239724 AN: 251366 AF XY: 0.958

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 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.: 30 AF XY: 0.961 AC XY: 698098 AN XY: 726056

African (AFR) AF: 0.717 AC: 23936 AN: 33394

American (AMR) AF: 0.958 AC: 42842 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 25442 AN: 26102

East Asian (EAS) AF: 1.00 AC: 39673 AN: 39674

South Asian (SAS) AF: 0.987 AC: 85065 AN: 86208

European-Finnish (FIN) AF: 0.969 AC: 51720 AN: 53366

Middle Eastern (MID) AF: 0.906 AC: 5219 AN: 5760

European-Non Finnish (NFE) AF: 0.964 AC: 1069584 AN: 1109786

Other (OTH) AF: 0.950 AC: 57269 AN: 60302

GnomAD4 genome AF: 0.900 AC: 136967 AN: 152210 Hom.: 62505 Cov.: 32 AF XY: 0.903 AC XY: 67247 AN XY: 74430

African (AFR) AF: 0.731 AC: 30324 AN: 41472

American (AMR) AF: 0.944 AC: 14439 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.980 AC: 3403 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5185 AN: 5186

South Asian (SAS) AF: 0.989 AC: 4776 AN: 4830

European-Finnish (FIN) AF: 0.964 AC: 10229 AN: 10606

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.964 AC: 65594 AN: 68030

Other (OTH) AF: 0.911 AC: 1925 AN: 2112

Alfa AF: 0.939 Hom.: 91629

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

Submissions by phenotype

not provided Benign:3

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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. -

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	-0.82
CADD	Benign	7.1
DANN	Benign	0.64
PhyloP100		0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs480760; hg19: chr3-195798258;