Genetic Variant TF:c.1203+1453C>T (chr3-133760782-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+1453C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 162,034 control chromosomes in the GnomAD database, including 7,160 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 0.28 ( 6994 hom., cov: 33)

Exomes 𝑓: 0.17 ( 166 hom. )

Consequence

TF
NM_001063.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0290

Publications

9 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=-0.62).

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
TF	NM_001063.4 link	c.1203+1453C>T	intron_variant	Intron 9 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2 link	c.1071+1453C>T	intron_variant	Intron 15 of 22		NP_001341632.2
TF	NM_001354704.2 link	c.822+1453C>T	intron_variant	Intron 8 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9 link	c.1203+1453C>T		intron_variant	Intron 9 of 16	1	NM_001063.4	ENSP00000385834.3
ACSL3P1	ENST00000474389.1 link	n.483C>T		non_coding_transcript_exon_variant	Exon 1 of 2	6

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

42950

AN:

151990

Hom.:

6988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.373

Gnomad ASJ

AF:

0.286

Gnomad EAS

AF:

0.425

Gnomad SAS

AF:

0.423

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.335

Gnomad OTH

AF:

0.296

GnomAD4 exome

AF:

0.170

AC:

1684

AN:

9926

Hom.:

166

Cov.:

AF XY:

0.168

AC XY:

928

AN XY:

5538

show subpopulations

African (AFR)

AF:

0.0300

AC:

AN:

100

American (AMR)

AF:

0.193

AC:

AN:

466

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

AN:

226

East Asian (EAS)

AF:

0.204

AC:

AN:

216

South Asian (SAS)

AF:

0.154

AC:

AN:

518

European-Finnish (FIN)

AF:

0.200

AC:

851

AN:

4260

Middle Eastern (MID)

AF:

0.0515

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.145

AC:

507

AN:

3500

Other (OTH)

AF:

0.171

AC:

AN:

368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

107

160

214

267

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:

0.283

AC:

42984

AN:

152108

Hom.:

6994

Cov.:

AF XY:

0.286

AC XY:

21257

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.126

AC:

5234

AN:

41510

American (AMR)

AF:

0.374

AC:

5720

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

992

AN:

3468

East Asian (EAS)

AF:

0.424

AC:

2193

AN:

5168

South Asian (SAS)

AF:

0.422

AC:

2037

AN:

4824

European-Finnish (FIN)

AF:

0.287

AC:

3030

AN:

10562

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.335

AC:

22796

AN:

67976

Other (OTH)

AF:

0.298

AC:

629

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1515

3030

4545

6060

7575

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.254

Hom.:

1680

Bravo

AF:

0.281

Asia WGS

AF:

0.393

AC:

1365

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.2

(source)

DANN

Benign

0.61

PhyloP100

0.029

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over