Genetic Variant NM_001128148.3:c.*1837A>G (chr3-196050105-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001128148.3(TFRC):c.*1837A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 230,654 control chromosomes in the GnomAD database, including 11,404 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 7737 hom., cov: 32)

Exomes 𝑓: 0.30 ( 3667 hom. )

Consequence

TFRC
NM_001128148.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0270

Publications

22 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:

ENSG00000286168 (HGNC:):

ENSG00000286168 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFRC	NM_001128148.3 link	c.*1837A>G		3_prime_UTR_variant	Exon 19 of 19	ENST00000360110.9	NP_001121620.1	P02786Q7Z3E0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFRC	ENST00000360110.9 link	c.*1837A>G		3_prime_UTR_variant	Exon 19 of 19	1	NM_001128148.3	ENSP00000353224.4		P02786

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48101

AN:

151858

Hom.:

7722

Cov.:

show subpopulations

Gnomad AFR

AF:

0.314

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.381

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.350

Gnomad FIN

AF:

0.369

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.293

GnomAD4 exome

AF:

0.302

AC:

23751

AN:

78678

Hom.:

3667

Cov.:

AF XY:

0.306

AC XY:

11091

AN XY:

36200

show subpopulations

African (AFR)

AF:

0.311

AC:

1175

AN:

3778

American (AMR)

AF:

0.270

AC:

652

AN:

2418

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

1906

AN:

4982

East Asian (EAS)

AF:

0.216

AC:

2399

AN:

11106

South Asian (SAS)

AF:

0.351

AC:

240

AN:

684

European-Finnish (FIN)

AF:

0.327

AC:

AN:

Middle Eastern (MID)

AF:

0.272

AC:

129

AN:

474

European-Non Finnish (NFE)

AF:

0.314

AC:

15241

AN:

48606

Other (OTH)

AF:

0.303

AC:

1992

AN:

6578

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

833

1667

2500

3334

4167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<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:

0.317

AC:

48159

AN:

151976

Hom.:

7737

Cov.:

AF XY:

0.319

AC XY:

23677

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.315

AC:

13046

AN:

41442

American (AMR)

AF:

0.283

AC:

4320

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.381

AC:

1322

AN:

3468

East Asian (EAS)

AF:

0.173

AC:

895

AN:

5174

South Asian (SAS)

AF:

0.348

AC:

1678

AN:

4822

European-Finnish (FIN)

AF:

0.369

AC:

3887

AN:

10544

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.322

AC:

21893

AN:

67946

Other (OTH)

AF:

0.291

AC:

616

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1658

3315

4973

6630

8288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

476

952

1428

1904

2380

<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:

0.319

Hom.:

24647

Bravo

AF:

0.307

Asia WGS

AF:

0.251

AC:

873

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.8

(source)

DANN

Benign

0.70

PhyloP100

-0.027

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over