dbSNP rs9846149: TFRC:c.1469-190G>C (chr3-196060437-C-G) – 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.1469-190G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 576,184 control chromosomes in the GnomAD database, including 86,710 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 19348 hom., cov: 31)

Exomes 𝑓: 0.55 ( 67362 hom. )

Consequence

TFRC
NM_001128148.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.412

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 3-196060437-C-G is Benign according to our data. Variant chr3-196060437-C-G is described in ClinVar as Benign. ClinVar VariationId is 1280043.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 rank	MANE	Protein	UniProt
TFRC	NM_001128148.3 link	c.1469-190G>C		intron_variant	Intron 13 of 18	ENST00000360110.9	NP_001121620.1	P02786Q7Z3E0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFRC	ENST00000360110.9 link	c.1469-190G>C		intron_variant	Intron 13 of 18	1	NM_001128148.3	ENSP00000353224.4		P02786

Frequencies

GnomAD3 genomes

AF:

0.481

AC:

73002

AN:

151836

Hom.:

19351

Cov.:

show subpopulations

Gnomad AFR

AF:

0.289

Gnomad AMI

AF:

0.384

Gnomad AMR

AF:

0.450

Gnomad ASJ

AF:

0.557

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.513

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.608

Gnomad OTH

AF:

0.520

GnomAD4 exome

AF:

0.549

AC:

232833

AN:

424230

Hom.:

67362

Cov.:

AF XY:

0.549

AC XY:

123784

AN XY:

225448

show subpopulations

African (AFR)

AF:

0.290

AC:

3355

AN:

11580

American (AMR)

AF:

0.419

AC:

7156

AN:

17070

Ashkenazi Jewish (ASJ)

AF:

0.543

AC:

6939

AN:

12778

East Asian (EAS)

AF:

0.209

AC:

6007

AN:

28714

South Asian (SAS)

AF:

0.525

AC:

23153

AN:

44124

European-Finnish (FIN)

AF:

0.555

AC:

16077

AN:

28942

Middle Eastern (MID)

AF:

0.661

AC:

1475

AN:

2230

European-Non Finnish (NFE)

AF:

0.611

AC:

155469

AN:

254580

Other (OTH)

AF:

0.545

AC:

13202

AN:

24212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

4499

8997

13496

17994

22493

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

656

1312

1968

2624

3280

<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:

0.480

AC:

73011

AN:

151954

Hom.:

19348

Cov.:

AF XY:

0.477

AC XY:

35394

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.289

AC:

11958

AN:

41444

American (AMR)

AF:

0.449

AC:

6856

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.557

AC:

1933

AN:

3470

East Asian (EAS)

AF:

0.167

AC:

866

AN:

5174

South Asian (SAS)

AF:

0.514

AC:

2476

AN:

4814

European-Finnish (FIN)

AF:

0.569

AC:

6003

AN:

10544

Middle Eastern (MID)

AF:

0.602

AC:

177

AN:

294

European-Non Finnish (NFE)

AF:

0.608

AC:

41311

AN:

67936

Other (OTH)

AF:

0.514

AC:

1084

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1738

3476

5214

6952

8690

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

656

1312

1968

2624

3280

<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:

0.538

Hom.:

2942

Bravo

AF:

0.459

Asia WGS

AF:

0.363

AC:

1265

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 2021

GeneDx

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

4.4

(source)

DANN

Benign

0.74

PhyloP100

0.41

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over