Genetic Variant NM_001063.4:c.1048+62C>T (chr3-133758008-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.1048+62C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,542,188 control chromosomes in the GnomAD database, including 93,819 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 ( 7473 hom., cov: 32)

Exomes 𝑓: 0.35 ( 86346 hom. )

Consequence

TF
NM_001063.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.214

Publications

14 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:

Genome browser will be placed here

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 (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4 link	c.1048+62C>T	intron_variant	Intron 8 of 16	ENST00000402696.9	NP_001054.2	P02787Q06AH7A0PJA6
TF	NM_001354703.2 link	c.916+62C>T	intron_variant	Intron 14 of 22		NP_001341632.2
TF	NM_001354704.2 link	c.667+62C>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.1048+62C>T		intron_variant	Intron 8 of 16	1	NM_001063.4	ENSP00000385834.3		P02787
TF	ENST00000485977.1 link	n.*104+62C>T		intron_variant	Intron 4 of 4	3		ENSP00000418716.1		F8WC57

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

45239

AN:

151822

Hom.:

7467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.165

Gnomad AMI

AF:

0.321

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.296

Gnomad EAS

AF:

0.426

Gnomad SAS

AF:

0.423

Gnomad FIN

AF:

0.294

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.342

Gnomad OTH

AF:

0.308

GnomAD4 exome

AF:

0.348

AC:

483588

AN:

1390248

Hom.:

86346

AF XY:

0.351

AC XY:

243645

AN XY:

694070

show subpopulations

African (AFR)

AF:

0.156

AC:

4980

AN:

31938

American (AMR)

AF:

0.466

AC:

19941

AN:

42814

Ashkenazi Jewish (ASJ)

AF:

0.291

AC:

7401

AN:

25430

East Asian (EAS)

AF:

0.435

AC:

17017

AN:

39118

South Asian (SAS)

AF:

0.432

AC:

36069

AN:

83474

European-Finnish (FIN)

AF:

0.309

AC:

16248

AN:

52612

Middle Eastern (MID)

AF:

0.296

AC:

1340

AN:

4526

European-Non Finnish (NFE)

AF:

0.343

AC:

361128

AN:

1052446

Other (OTH)

AF:

0.336

AC:

19464

AN:

57890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

15502

31004

46507

62009

77511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.298

AC:

45276

AN:

151940

Hom.:

7473

Cov.:

AF XY:

0.300

AC XY:

22286

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.165

AC:

6846

AN:

41412

American (AMR)

AF:

0.380

AC:

5807

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.296

AC:

1028

AN:

3472

East Asian (EAS)

AF:

0.425

AC:

2193

AN:

5160

South Asian (SAS)

AF:

0.422

AC:

2035

AN:

4820

European-Finnish (FIN)

AF:

0.294

AC:

3097

AN:

10550

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.342

AC:

23254

AN:

67940

Other (OTH)

AF:

0.310

AC:

654

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1547

3095

4642

6190

7737

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.313

Hom.:

10385

Bravo

AF:

0.298

Asia WGS

AF:

0.393

AC:

1366

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.3

(source)

DANN

Benign

0.57

PhyloP100

-0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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NM_001063.4:c.1048+62C>T

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