dbSNP rs8177253: TF:c.1203+2019C>T (chr3-133761348-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.1203+2019C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 154,176 control chromosomes in the GnomAD database, including 8,078 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 0.32 ( 7922 hom., cov: 32)

Exomes 𝑓: 0.37 ( 156 hom. )

Consequence

TF
NM_001063.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.92

Publications

13 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 links:

ACSL3P1 (HGNC:56529): (ACSL3 pseudogene 1)

ACSL3P1 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 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.1203+2019C>T	intron	N/A	NP_001054.2	P02787
TF	NM_001354703.2		c.1071+2019C>T	intron	N/A	NP_001341632.2
TF	NM_001354704.2		c.822+2019C>T	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.1203+2019C>T	intron	N/A	ENSP00000385834.3	P02787
TF	ENST00000877249.1		c.555+2019C>T	intron	N/A	ENSP00000547308.1
TF	ENST00000877246.1		c.217-2834C>T	intron	N/A	ENSP00000547305.1

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

47964

AN:

151710

Hom.:

7910

Cov.:

show subpopulations

Gnomad AFR

AF:

0.242

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.387

Gnomad ASJ

AF:

0.286

Gnomad EAS

AF:

0.426

Gnomad SAS

AF:

0.423

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.336

Gnomad OTH

AF:

0.319

GnomAD4 exome

AF:

0.371

AC:

870

AN:

2348

Hom.:

156

Cov.:

AF XY:

0.378

AC XY:

565

AN XY:

1496

show subpopulations

African (AFR)

AF:

0.214

AC:

AN:

American (AMR)

AF:

0.477

AC:

106

AN:

222

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

AN:

East Asian (EAS)

AF:

0.444

AC:

AN:

108

South Asian (SAS)

AF:

0.514

AC:

113

AN:

220

European-Finnish (FIN)

AF:

0.327

AC:

112

AN:

342

Middle Eastern (MID)

AF:

0.333

AC:

AN:

European-Non Finnish (NFE)

AF:

0.345

AC:

430

AN:

1246

Other (OTH)

AF:

0.361

AC:

AN:

122

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.316

AC:

48018

AN:

151828

Hom.:

7922

Cov.:

AF XY:

0.318

AC XY:

23572

AN XY:

74178

show subpopulations

African (AFR)

AF:

0.243

AC:

10051

AN:

41408

American (AMR)

AF:

0.387

AC:

5909

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

990

AN:

3466

East Asian (EAS)

AF:

0.425

AC:

2194

AN:

5158

South Asian (SAS)

AF:

0.423

AC:

2026

AN:

4792

European-Finnish (FIN)

AF:

0.286

AC:

3010

AN:

10520

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.336

AC:

22806

AN:

67914

Other (OTH)

AF:

0.320

AC:

676

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1635

3270

4905

6540

8175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

502

1004

1506

2008

2510

<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:

0.331

Hom.:

12955

Bravo

AF:

0.320

Asia WGS

AF:

0.402

AC:

1399

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.62

(source)

DANN

Benign

0.65

PhyloP100

2.9

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)

0.0

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