Genetic Variant TF:c.2062+471T>C (chr3-133777709-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.2062+471T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 173,654 control chromosomes in the GnomAD database, including 8,700 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 0.30 ( 7410 hom., cov: 33)

Exomes 𝑓: 0.32 ( 1290 hom. )

Consequence

TF
NM_001063.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.549

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=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.406 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.2062+471T>C	intron	N/A	NP_001054.2	P02787
TF	NM_001354703.2		c.1930+471T>C	intron	N/A	NP_001341632.2
TF	NM_001354704.2		c.1681+471T>C	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.2062+471T>C	intron	N/A	ENSP00000385834.3	P02787
TF	ENST00000467842.1	TSL:1	n.3527T>C	non_coding_transcript_exon	Exon 2 of 2
TF	ENST00000877249.1		c.1414+471T>C	intron	N/A	ENSP00000547308.1

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45446

AN:

152024

Hom.:

7405

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.314

Gnomad AMR

AF:

0.380

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.419

Gnomad SAS

AF:

0.422

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.336

Gnomad OTH

AF:

0.306

GnomAD4 exome

AF:

0.321

AC:

6904

AN:

21512

Hom.:

1290

Cov.:

AF XY:

0.327

AC XY:

3586

AN XY:

10964

show subpopulations

African (AFR)

AF:

0.138

AC:

AN:

390

American (AMR)

AF:

0.413

AC:

1207

AN:

2922

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

AN:

352

East Asian (EAS)

AF:

0.354

AC:

511

AN:

1442

South Asian (SAS)

AF:

0.390

AC:

883

AN:

2266

European-Finnish (FIN)

AF:

0.277

AC:

161

AN:

582

Middle Eastern (MID)

AF:

0.297

AC:

AN:

European-Non Finnish (NFE)

AF:

0.295

AC:

3662

AN:

12402

Other (OTH)

AF:

0.306

AC:

331

AN:

1082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

206

412

619

825

1031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

276

368

460

<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:

0.299

AC:

45476

AN:

152142

Hom.:

7410

Cov.:

AF XY:

0.300

AC XY:

22348

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.185

AC:

7671

AN:

41524

American (AMR)

AF:

0.381

AC:

5818

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.271

AC:

941

AN:

3468

East Asian (EAS)

AF:

0.418

AC:

2164

AN:

5180

South Asian (SAS)

AF:

0.421

AC:

2026

AN:

4814

European-Finnish (FIN)

AF:

0.286

AC:

3027

AN:

10574

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.336

AC:

22821

AN:

67978

Other (OTH)

AF:

0.308

AC:

651

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1608

3216

4824

6432

8040

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

482

964

1446

1928

2410

<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:

0.201

Hom.:

529

Bravo

AF:

0.300

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.3

(source)

DANN

Benign

0.85

PhyloP100

-0.55

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over