Genetic Variant TF:c.503-204C>G (chr3-133755159-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001063.4(TF):c.503-204C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,148 control chromosomes in the GnomAD database, including 6,853 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 0.29 ( 6853 hom., cov: 33)

Consequence

TF
NM_001063.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.334

Publications

6 publications found

Variant links:

Genes affected

TF (HGNC:11740): (transferrin) This gene encodes a glycoprotein with an approximate molecular weight of 76.5 kDa. It is thought to have been created as a result of an ancient gene duplication event that led to generation of homologous C and N-terminal domains each of which binds one ion of ferric iron. The function of this protein is to transport iron from the intestine, reticuloendothelial system, and liver parenchymal cells to all proliferating cells in the body. This protein may also have a physiologic role as granulocyte/pollen-binding protein (GPBP) involved in the removal of certain organic matter and allergens from serum. [provided by RefSeq, Sep 2009]

TF Gene-Disease associations (from GenCC):

atransferrinemia
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Genomics England PanelApp

TF links:

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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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001063.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TF	NM_001063.4	MANE Select	c.503-204C>G	intron	N/A	NP_001054.2	P02787
TF	NM_001354703.2		c.371-204C>G	intron	N/A	NP_001341632.2
TF	NM_001354704.2		c.122-204C>G	intron	N/A	NP_001341633.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TF	ENST00000402696.9	TSL:1 MANE Select	c.503-204C>G	intron	N/A	ENSP00000385834.3	P02787
TF	ENST00000877249.1		c.44-1672C>G	intron	N/A	ENSP00000547308.1
TF	ENST00000877246.1		c.216+6575C>G	intron	N/A	ENSP00000547305.1

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43811

AN:

152030

Hom.:

6851

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.350

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.441

Gnomad SAS

AF:

0.407

Gnomad FIN

AF:

0.299

Gnomad MID

AF:

0.140

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.280

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

GnomAD4 genome

AF:

0.288

AC:

43835

AN:

152148

Hom.:

6853

Cov.:

AF XY:

0.290

AC XY:

21589

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.191

AC:

7911

AN:

41522

American (AMR)

AF:

0.351

AC:

5366

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

834

AN:

3470

East Asian (EAS)

AF:

0.440

AC:

2271

AN:

5166

South Asian (SAS)

AF:

0.406

AC:

1959

AN:

4824

European-Finnish (FIN)

AF:

0.299

AC:

3160

AN:

10572

Middle Eastern (MID)

AF:

0.144

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.315

AC:

21411

AN:

67978

Other (OTH)

AF:

0.281

AC:

593

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1586

3173

4759

6346

7932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.299

Hom.:

976

Bravo

AF:

0.287

Asia WGS

AF:

0.411

AC:

1428

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.40

(source)

DANN

Benign

0.59

PhyloP100

-0.33

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over