chr3-196071387-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

9 publications found

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 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)

TFRC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128148.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TFRC	NM_001128148.3	MANE Select	c.687+9A>G	intron	N/A	NP_001121620.1
TFRC	NM_003234.4		c.687+9A>G	intron	N/A	NP_003225.2
TFRC	NM_001313965.2		c.444+9A>G	intron	N/A	NP_001300894.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TFRC	ENST00000360110.9	TSL:1 MANE Select	c.687+9A>G	intron	N/A	ENSP00000353224.4
TFRC	ENST00000392396.7	TSL:1	c.687+9A>G	intron	N/A	ENSP00000376197.3
TFRC	ENST00000420415.5	TSL:1	c.444+9A>G	intron	N/A	ENSP00000390133.1

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

GnomAD2 exomes

AF:

0.954

AC:

239724

AN:

251366

AF XY:

0.958

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 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

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

2792

5584

8377

11169

13961

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21566

43132

64698

86264

107830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.900

AC:

136967

AN:

152210

Hom.:

62505

Cov.:

AF XY:

0.903

AC XY:

67247

AN XY:

74430

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

621

1243

1864

2486

3107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

900

1800

2700

3600

4500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.1

(source)

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over