NM_001063.4:c.624G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001063.4(TF):c.624G>A(p.Ser208Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,613,820 control chromosomes in the GnomAD database, including 85,910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6419 hom., cov: 32)

Exomes 𝑓: 0.32 ( 79491 hom. )

Consequence

TF
NM_001063.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.60

Publications

23 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 3-133755484-G-A is Benign according to our data. Variant chr3-133755484-G-A is described in ClinVar as Benign. ClinVar VariationId is 343436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.6 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4 link	c.624G>A	p.Ser208Ser	synonymous_variant	Exon 5 of 17	ENST00000402696.9	NP_001054.2	P02787Q06AH7A0PJA6
TF	NM_001354703.2 link	c.492G>A	p.Ser164Ser	synonymous_variant	Exon 11 of 23		NP_001341632.2
TF	NM_001354704.2 link	c.243G>A	p.Ser81Ser	synonymous_variant	Exon 4 of 16		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9 link	c.624G>A	p.Ser208Ser	synonymous_variant	Exon 5 of 17	1	NM_001063.4	ENSP00000385834.3		P02787

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41188

AN:

152044

Hom.:

6418

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.315

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.441

Gnomad SAS

AF:

0.406

Gnomad FIN

AF:

0.299

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.270

GnomAD2 exomes

AF:

0.335

AC:

83312

AN:

248742

AF XY:

0.336

show subpopulations

Gnomad AFR exome

AF:

0.127

Gnomad AMR exome

AF:

0.455

Gnomad ASJ exome

AF:

0.237

Gnomad EAS exome

AF:

0.420

Gnomad FIN exome

AF:

0.303

Gnomad NFE exome

AF:

0.311

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

AF:

0.323

AC:

472839

AN:

1461658

Hom.:

79491

Cov.:

AF XY:

0.326

AC XY:

236940

AN XY:

727142

show subpopulations

African (AFR)

AF:

0.116

AC:

3886

AN:

33480

American (AMR)

AF:

0.442

AC:

19749

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

6244

AN:

26136

East Asian (EAS)

AF:

0.473

AC:

18793

AN:

39694

South Asian (SAS)

AF:

0.405

AC:

34967

AN:

86248

European-Finnish (FIN)

AF:

0.304

AC:

16226

AN:

53330

Middle Eastern (MID)

AF:

0.192

AC:

1108

AN:

5768

European-Non Finnish (NFE)

AF:

0.318

AC:

353484

AN:

1111898

Other (OTH)

AF:

0.304

AC:

18382

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

19801

39603

59404

79206

99007

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11684

23368

35052

46736

58420

<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:

0.271

AC:

41202

AN:

152162

Hom.:

6419

Cov.:

AF XY:

0.274

AC XY:

20403

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.131

AC:

5432

AN:

41528

American (AMR)

AF:

0.344

AC:

5258

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

833

AN:

3470

East Asian (EAS)

AF:

0.440

AC:

2274

AN:

5172

South Asian (SAS)

AF:

0.405

AC:

1954

AN:

4820

European-Finnish (FIN)

AF:

0.299

AC:

3160

AN:

10576

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.315

AC:

21390

AN:

67980

Other (OTH)

AF:

0.271

AC:

573

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1484

2968

4453

5937

7421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<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:

0.282

Hom.:

11237

Bravo

AF:

0.268

Asia WGS

AF:

0.404

AC:

1405

AN:

3478

EpiCase

AF:

0.300

EpiControl

AF:

0.296

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Atransferrinemia

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.87

(source)

DANN

Benign

0.83

PhyloP100

-3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over