Genetic Variant TFRC:c.1468+39A>G (chr3-196062543-T-C) – ACMG Classification: Benign (-20 pts)

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.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

Publications

7 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: DEFINITIVE, MODERATE, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen

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=-0.8).

BP6

Variant 3-196062543-T-C is Benign according to our data. Variant chr3-196062543-T-C is described in ClinVar as Benign. ClinVar VariationId 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.

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	UniProt
TFRC	NM_001128148.3	MANE Select	c.1468+39A>G	intron	N/A	NP_001121620.1	P02786
TFRC	NM_003234.4		c.1468+39A>G	intron	N/A	NP_003225.2	P02786
TFRC	NM_001313965.2		c.1225+39A>G	intron	N/A	NP_001300894.1	G3V0E5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TFRC	ENST00000360110.9	TSL:1 MANE Select	c.1468+39A>G	intron	N/A	ENSP00000353224.4	P02786
TFRC	ENST00000392396.7	TSL:1	c.1468+39A>G	intron	N/A	ENSP00000376197.3	P02786
TFRC	ENST00000420415.5	TSL:1	c.1225+39A>G	intron	N/A	ENSP00000390133.1	G3V0E5

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

GnomAD2 exomes

AF:

0.503

AC:

119475

AN:

237402

AF XY:

0.515

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 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

African (AFR)

AF:

0.283

AC:

9046

AN:

32004

American (AMR)

AF:

0.380

AC:

15193

AN:

39984

Ashkenazi Jewish (ASJ)

AF:

0.546

AC:

13915

AN:

25470

East Asian (EAS)

AF:

0.200

AC:

7908

AN:

39528

South Asian (SAS)

AF:

0.527

AC:

43649

AN:

82804

European-Finnish (FIN)

AF:

0.560

AC:

29794

AN:

53180

Middle Eastern (MID)

AF:

0.663

AC:

3712

AN:

5602

European-Non Finnish (NFE)

AF:

0.614

AC:

666400

AN:

1084932

Other (OTH)

AF:

0.558

AC:

32931

AN:

59008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

15423

30845

46268

61690

77113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17536

35072

52608

70144

87680

<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:

0.482

AC:

73322

AN:

152168

Hom.:

19438

Cov.:

AF XY:

0.478

AC XY:

35541

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.294

AC:

12204

AN:

41512

American (AMR)

AF:

0.449

AC:

6869

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.557

AC:

1933

AN:

3472

East Asian (EAS)

AF:

0.166

AC:

862

AN:

5182

South Asian (SAS)

AF:

0.514

AC:

2478

AN:

4824

European-Finnish (FIN)

AF:

0.569

AC:

6014

AN:

10578

Middle Eastern (MID)

AF:

0.602

AC:

177

AN:

294

European-Non Finnish (NFE)

AF:

0.608

AC:

41344

AN:

67990

Other (OTH)

AF:

0.515

AC:

1089

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1830

3659

5489

7318

9148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

660

1320

1980

2640

3300

<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:

0.551

Hom.:

7973

Bravo

AF:

0.460

Asia WGS

AF:

0.363

AC:

1265

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

TFRC-related combined immunodeficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.1

(source)

DANN

Benign

0.66

PhyloP100

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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

Computational scores

Splicing

Publications

Other links and lift over