3-133756878-C-T

Position:

chr3-133756878-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001063.4(TF):c.739C>T(p.Leu247Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,614,108 control chromosomes in the GnomAD database, including 10,732 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1030 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9702 hom. )

Consequence

TF
NM_001063.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.268

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 3-133756878-C-T is Benign according to our data. Variant chr3-133756878-C-T is described in ClinVar as [Benign]. Clinvar id is 343439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.268 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TF	NM_001063.4 link	c.739C>T	p.Leu247Leu	synonymous_variant	7/17	ENST00000402696.9	NP_001054.2	P02787Q06AH7A0PJA6
TF	NM_001354703.2 link	c.607C>T	p.Leu203Leu	synonymous_variant	13/23		NP_001341632.2
TF	NM_001354704.2 link	c.358C>T	p.Leu120Leu	synonymous_variant	6/16		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TF	ENST00000402696.9 link	c.739C>T	p.Leu247Leu	synonymous_variant	7/17	1	NM_001063.4	ENSP00000385834.3	P02787
TF	ENST00000482271.5 link	c.358C>T	p.Leu120Leu	synonymous_variant	6/6	4		ENSP00000419338.1	C9JVG0
TF	ENST00000485977.1 link	n.158-54C>T		intron_variant		3		ENSP00000418716.1	F8WC57

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16433

AN:

152114

Hom.:

1028

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0632

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.246

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.174

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.110

GnomAD3 exomes

AF:

0.131

AC:

32867

AN:

251486

Hom.:

2505

AF XY:

0.131

AC XY:

17866

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0617

Gnomad AMR exome

AF:

0.132

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.267

Gnomad SAS exome

AF:

0.148

Gnomad FIN exome

AF:

0.167

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.136

GnomAD4 exome

AF:

0.109

AC:

159010

AN:

1461874

Hom.:

9702

Cov.:

AF XY:

0.110

AC XY:

80024

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0596

Gnomad4 AMR exome

AF:

0.133

Gnomad4 ASJ exome

AF:

0.122

Gnomad4 EAS exome

AF:

0.225

Gnomad4 SAS exome

AF:

0.147

Gnomad4 FIN exome

AF:

0.166

Gnomad4 NFE exome

AF:

0.0983

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.108

AC:

16433

AN:

152234

Hom.:

1030

Cov.:

AF XY:

0.113

AC XY:

8432

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0631

Gnomad4 AMR

AF:

0.133

Gnomad4 ASJ

AF:

0.118

Gnomad4 EAS

AF:

0.246

Gnomad4 SAS

AF:

0.159

Gnomad4 FIN

AF:

0.174

Gnomad4 NFE

AF:

0.105

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.109

Hom.:

2027

Bravo

AF:

0.104

Asia WGS

AF:

0.200

AC:

692

AN:

3478

EpiCase

AF:

0.104

EpiControl

AF:

0.107

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Atransferrinemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

TF-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.5

DANN

Benign

0.83

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over