dbSNP rs1880669: TF:c.1298-23T>C (chr3-133764852-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001063.4(TF):c.1298-23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,609,006 control chromosomes in the GnomAD database, including 272,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.52 ( 21560 hom., cov: 33)

Exomes 𝑓: 0.58 ( 250525 hom. )

Consequence

TF
NM_001063.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.705

Publications

15 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: ClinGen, PanelApp Australia, Genomics England PanelApp, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

TF links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001063.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 3-133764852-T-C is Benign according to our data. Variant chr3-133764852-T-C is described in ClinVar as Benign. ClinVar VariationId is 4684725.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.587 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.1298-23T>C	intron	N/A	NP_001054.2	P02787
TF	NM_001354703.2		c.1166-23T>C	intron	N/A	NP_001341632.2
TF	NM_001354704.2		c.917-23T>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.1298-23T>C	intron	N/A	ENSP00000385834.3	P02787
TF	ENST00000877249.1		c.650-23T>C	intron	N/A	ENSP00000547308.1
TF	ENST00000877246.1		c.311-23T>C	intron	N/A	ENSP00000547305.1

Frequencies

GnomAD3 genomes

AF:

0.523

AC:

79468

AN:

151990

Hom.:

21550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.368

Gnomad AMI

AF:

0.708

Gnomad AMR

AF:

0.563

Gnomad ASJ

AF:

0.519

Gnomad EAS

AF:

0.490

Gnomad SAS

AF:

0.566

Gnomad FIN

AF:

0.606

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.592

Gnomad OTH

AF:

0.536

GnomAD2 exomes

AF:

0.565

AC:

141565

AN:

250474

AF XY:

0.569

show subpopulations

Gnomad AFR exome

AF:

0.368

Gnomad AMR exome

AF:

0.607

Gnomad ASJ exome

AF:

0.512

Gnomad EAS exome

AF:

0.460

Gnomad FIN exome

AF:

0.614

Gnomad NFE exome

AF:

0.588

Gnomad OTH exome

AF:

0.555

GnomAD4 exome

AF:

0.584

AC:

851055

AN:

1456898

Hom.:

250525

Cov.:

AF XY:

0.584

AC XY:

423369

AN XY:

724888

show subpopulations

African (AFR)

AF:

0.362

AC:

12092

AN:

33366

American (AMR)

AF:

0.602

AC:

26823

AN:

44578

Ashkenazi Jewish (ASJ)

AF:

0.512

AC:

13359

AN:

26092

East Asian (EAS)

AF:

0.507

AC:

20125

AN:

39658

South Asian (SAS)

AF:

0.581

AC:

49810

AN:

85778

European-Finnish (FIN)

AF:

0.609

AC:

32530

AN:

53398

Middle Eastern (MID)

AF:

0.534

AC:

3069

AN:

5750

European-Non Finnish (NFE)

AF:

0.595

AC:

659131

AN:

1108054

Other (OTH)

AF:

0.566

AC:

34116

AN:

60224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

14733

29467

44200

58934

73667

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17950

35900

53850

71800

89750

<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:

0.523

AC:

79500

AN:

152108

Hom.:

21560

Cov.:

AF XY:

0.523

AC XY:

38912

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.368

AC:

15268

AN:

41470

American (AMR)

AF:

0.563

AC:

8617

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.519

AC:

1801

AN:

3470

East Asian (EAS)

AF:

0.489

AC:

2531

AN:

5180

South Asian (SAS)

AF:

0.565

AC:

2722

AN:

4814

European-Finnish (FIN)

AF:

0.606

AC:

6413

AN:

10580

Middle Eastern (MID)

AF:

0.517

AC:

152

AN:

294

European-Non Finnish (NFE)

AF:

0.592

AC:

40220

AN:

67972

Other (OTH)

AF:

0.535

AC:

1130

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1950

3900

5850

7800

9750

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<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:

0.566

Hom.:

94599

Bravo

AF:

0.513

Asia WGS

AF:

0.523

AC:

1817

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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