dbSNP rs557527: TFRC:c.1900-280C>T (chr3-196053838-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001128148.3(TFRC):c.1900-280C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,034 control chromosomes in the GnomAD database, including 7,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.32 ( 7667 hom., cov: 32)

Consequence

TFRC
NM_001128148.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.218

Publications

4 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:

ENSG00000286168 (HGNC:):

ENSG00000286168 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-196053838-G-A is Benign according to our data. Variant chr3-196053838-G-A is described in ClinVar as Benign. ClinVar VariationId is 1280483.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.327 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.1900-280C>T	intron	N/A	NP_001121620.1	P02786
TFRC	NM_003234.4		c.1900-280C>T	intron	N/A	NP_003225.2	P02786
TFRC	NM_001313965.2		c.1657-280C>T	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.1900-280C>T	intron	N/A	ENSP00000353224.4	P02786
TFRC	ENST00000392396.7	TSL:1	c.1900-280C>T	intron	N/A	ENSP00000376197.3	P02786
TFRC	ENST00000420415.5	TSL:1	c.1657-280C>T	intron	N/A	ENSP00000390133.1	G3V0E5

Frequencies

GnomAD3 genomes

AF:

0.315

AC:

47858

AN:

151916

Hom.:

7656

Cov.:

show subpopulations

Gnomad AFR

AF:

0.309

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.381

Gnomad EAS

AF:

0.171

Gnomad SAS

AF:

0.343

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.292

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.315

AC:

47905

AN:

152034

Hom.:

7667

Cov.:

AF XY:

0.317

AC XY:

23562

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.309

AC:

12821

AN:

41440

American (AMR)

AF:

0.282

AC:

4314

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.381

AC:

1320

AN:

3468

East Asian (EAS)

AF:

0.171

AC:

888

AN:

5180

South Asian (SAS)

AF:

0.341

AC:

1644

AN:

4818

European-Finnish (FIN)

AF:

0.370

AC:

3904

AN:

10554

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.322

AC:

21903

AN:

67994

Other (OTH)

AF:

0.290

AC:

611

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1728

3456

5183

6911

8639

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

474

948

1422

1896

2370

<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:

0.326

Hom.:

1094

Bravo

AF:

0.305

Asia WGS

AF:

0.241

AC:

840

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.9

(source)

DANN

Benign

0.31

PhyloP100

0.22

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over