Genetic Variant NM_001063.4:c.1298-23T>C (chr3-133764852-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

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

Exomes 𝑓: 0.58 ( 250525 hom. )

Consequence

TF
NM_001063.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.705

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4 link	c.1298-23T>C	intron_variant	Intron 10 of 16	ENST00000402696.9	NP_001054.2	P02787Q06AH7A0PJA6
TF	NM_001354703.2 link	c.1166-23T>C	intron_variant	Intron 16 of 22		NP_001341632.2
TF	NM_001354704.2 link	c.917-23T>C	intron_variant	Intron 9 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9 link	c.1298-23T>C		intron_variant	Intron 10 of 16	1	NM_001063.4	ENSP00000385834.3		P02787

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

GnomAD3 exomes

AF:

0.565

AC:

141565

AN:

250474

Hom.:

40742

AF XY:

0.569

AC XY:

76916

AN XY:

135280

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 SAS exome

AF:

0.586

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

Gnomad4 AFR exome

AF:

0.362

Gnomad4 AMR exome

AF:

0.602

Gnomad4 ASJ exome

AF:

0.512

Gnomad4 EAS exome

AF:

0.507

Gnomad4 SAS exome

AF:

0.581

Gnomad4 FIN exome

AF:

0.609

Gnomad4 NFE exome

AF:

0.595

Gnomad4 OTH exome

AF:

0.566

GnomAD4 genome

AF:

0.523

AC:

79500

AN:

152108

Hom.:

21560

Cov.:

AF XY:

0.523

AC XY:

38912

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.368

Gnomad4 AMR

AF:

0.563

Gnomad4 ASJ

AF:

0.519

Gnomad4 EAS

AF:

0.489

Gnomad4 SAS

AF:

0.565

Gnomad4 FIN

AF:

0.606

Gnomad4 NFE

AF:

0.592

Gnomad4 OTH

AF:

0.535

Alfa

AF:

0.572

Hom.:

43302

Bravo

AF:

0.513

Asia WGS

AF:

0.523

AC:

1817

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over