Genetic Variant TF:c.1486+553C>T (chr3-133766986-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.1486+553C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,084 control chromosomes in the GnomAD database, including 5,351 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 0.26 ( 5351 hom., cov: 32)

Consequence

TF
NM_001063.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.133

Publications

7 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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
TF	NM_001063.4 link	c.1486+553C>T	intron_variant	Intron 12 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2 link	c.1354+553C>T	intron_variant	Intron 18 of 22		NP_001341632.2
TF	NM_001354704.2 link	c.1105+553C>T	intron_variant	Intron 11 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9 link	c.1486+553C>T		intron_variant	Intron 12 of 16	1	NM_001063.4	ENSP00000385834.3
TF	ENST00000461695.1 link	n.154+553C>T		intron_variant	Intron 1 of 6	3		ENSP00000419714.1

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39200

AN:

151966

Hom.:

5348

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.188

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.0672

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.253

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

GnomAD4 genome

AF:

0.258

AC:

39214

AN:

152084

Hom.:

5351

Cov.:

AF XY:

0.255

AC XY:

18937

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.310

AC:

12871

AN:

41476

American (AMR)

AF:

0.188

AC:

2871

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

811

AN:

3472

East Asian (EAS)

AF:

0.0674

AC:

348

AN:

5164

South Asian (SAS)

AF:

0.133

AC:

639

AN:

4816

European-Finnish (FIN)

AF:

0.316

AC:

3344

AN:

10578

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.255

AC:

17356

AN:

67980

Other (OTH)

AF:

0.250

AC:

528

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1479

2957

4436

5914

7393

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.241

Hom.:

5790

Bravo

AF:

0.252

Asia WGS

AF:

0.133

AC:

463

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.4

(source)

DANN

Benign

0.65

PhyloP100

-0.13

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over