Genetic Variant TF:c.1049-58C>T (chr3-133759117-C-T) – 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.1049-58C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00314 in 1,610,220 control chromosomes in the GnomAD database, including 141 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 0.016 ( 67 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 74 hom. )

Consequence

TF
NM_001063.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.788

Publications

2 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, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, 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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
TF	NM_001063.4 link	c.1049-58C>T	intron_variant	Intron 8 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2 link	c.917-58C>T	intron_variant	Intron 14 of 22		NP_001341632.2
TF	NM_001354704.2 link	c.668-58C>T	intron_variant	Intron 7 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9 link	c.1049-58C>T		intron_variant	Intron 8 of 16	1	NM_001063.4	ENSP00000385834.3
TF	ENST00000485977.1 link	n.*105-58C>T		intron_variant	Intron 4 of 4	3		ENSP00000418716.1

Frequencies

GnomAD3 genomes

AF:

0.0162

AC:

2458

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0562

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.0115

GnomAD4 exome

AF:

0.00178

AC:

2593

AN:

1457938

Hom.:

AF XY:

0.00150

AC XY:

1088

AN XY:

725558

show subpopulations

African (AFR)

AF:

0.0630

AC:

2103

AN:

33404

American (AMR)

AF:

0.00273

AC:

122

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.000101

AC:

AN:

39684

South Asian (SAS)

AF:

0.000256

AC:

AN:

85878

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52868

Middle Eastern (MID)

AF:

0.00233

AC:

AN:

5580

European-Non Finnish (NFE)

AF:

0.0000838

AC:

AN:

1109440

Other (OTH)

AF:

0.00392

AC:

236

AN:

60250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

139

278

418

557

696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<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:

0.0162

AC:

2468

AN:

152282

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1162

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0563

AC:

2340

AN:

41550

American (AMR)

AF:

0.00575

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000579

AC:

AN:

5182

South Asian (SAS)

AF:

0.000415

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68030

Other (OTH)

AF:

0.0114

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

114

228

343

457

571

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00791

Hom.:

Bravo

AF:

0.0187

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.6

(source)

DANN

Benign

0.79

PhyloP100

-0.79

Mutation Taster

=100/0

polymorphism

(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