Genetic Variant TF:c.43+372T>C (chr3-133746855-T-C) – 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.43+372T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,100 control chromosomes in the GnomAD database, including 9,580 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 0.35 ( 9580 hom., cov: 32)

Consequence

TF
NM_001063.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.760

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:

ENSG00000291042 (HGNC:):

ENSG00000291042 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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 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
TF	NM_001063.4	MANE Select	c.43+372T>C	intron	N/A	NP_001054.2
TF	NM_001354703.2		c.-89-1557T>C	intron	N/A	NP_001341632.2
TF	NM_001354704.2		c.-166+372T>C	intron	N/A	NP_001341633.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TF	ENST00000402696.9	TSL:1 MANE Select	c.43+372T>C	intron	N/A	ENSP00000385834.3
TF	ENST00000482271.5	TSL:4	c.-166+372T>C	intron	N/A	ENSP00000419338.1
TF	ENST00000466911.5	TSL:4	c.-90+606T>C	intron	N/A	ENSP00000417468.1

Frequencies

GnomAD3 genomes

AF:

0.350

AC:

53119

AN:

151982

Hom.:

9579

Cov.:

show subpopulations

Gnomad AFR

AF:

0.397

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.374

Gnomad ASJ

AF:

0.243

Gnomad EAS

AF:

0.415

Gnomad SAS

AF:

0.402

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.319

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

GnomAD4 genome

AF:

0.349

AC:

53147

AN:

152100

Hom.:

9580

Cov.:

AF XY:

0.349

AC XY:

25942

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.396

AC:

16439

AN:

41464

American (AMR)

AF:

0.375

AC:

5732

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

842

AN:

3468

East Asian (EAS)

AF:

0.413

AC:

2133

AN:

5160

South Asian (SAS)

AF:

0.401

AC:

1937

AN:

4826

European-Finnish (FIN)

AF:

0.305

AC:

3232

AN:

10580

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.322

AC:

21870

AN:

67990

Other (OTH)

AF:

0.319

AC:

674

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1774

3547

5321

7094

8868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<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:

0.336

Hom.:

11634

Bravo

AF:

0.356

Asia WGS

AF:

0.428

AC:

1486

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.2

(source)

DANN

Benign

0.41

PhyloP100

-0.76

PromoterAI

0.058

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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