chr3-133755484-G-A

Position:

chr3-133755484-G-A

Variant summary

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

The NM_001063.4(TF):c.624G>A(p.Ser208Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,613,820 control chromosomes in the GnomAD database, including 85,910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6419 hom., cov: 32)

Exomes 𝑓: 0.32 ( 79491 hom. )

Consequence

TF
NM_001063.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.60

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:

TF (HGNC:):

TF links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 3-133755484-G-A is Benign according to our data. Variant chr3-133755484-G-A is described in ClinVar as [Benign]. Clinvar id is 343436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-133755484-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.6 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TF	NM_001063.4 linkuse as main transcript	c.624G>A	p.Ser208Ser	synonymous_variant	5/17	ENST00000402696.9	NP_001054.2	P02787Q06AH7A0PJA6
TF	NM_001354703.2 linkuse as main transcript	c.492G>A	p.Ser164Ser	synonymous_variant	11/23		NP_001341632.2
TF	NM_001354704.2 linkuse as main transcript	c.243G>A	p.Ser81Ser	synonymous_variant	4/16		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TF	ENST00000402696.9 linkuse as main transcript	c.624G>A	p.Ser208Ser	synonymous_variant	5/17	1	NM_001063.4	ENSP00000385834.3	P02787
TF	ENST00000482271.5 linkuse as main transcript	c.243G>A	p.Ser81Ser	synonymous_variant	4/6	4		ENSP00000419338.1	C9JVG0
TF	ENST00000493011.5 linkuse as main transcript	n.672G>A		non_coding_transcript_exon_variant	5/5	2
TF	ENST00000485977.1 linkuse as main transcript	n.158-1448G>A		intron_variant		3		ENSP00000418716.1	F8WC57

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41188

AN:

152044

Hom.:

6418

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.315

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.441

Gnomad SAS

AF:

0.406

Gnomad FIN

AF:

0.299

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.270

GnomAD3 exomes

AF:

0.335

AC:

83312

AN:

248742

Hom.:

15279

AF XY:

0.336

AC XY:

45226

AN XY:

134660

show subpopulations

Gnomad AFR exome

AF:

0.127

Gnomad AMR exome

AF:

0.455

Gnomad ASJ exome

AF:

0.237

Gnomad EAS exome

AF:

0.420

Gnomad SAS exome

AF:

0.411

Gnomad FIN exome

AF:

0.303

Gnomad NFE exome

AF:

0.311

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

AF:

0.323

AC:

472839

AN:

1461658

Hom.:

79491

Cov.:

AF XY:

0.326

AC XY:

236940

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.116

Gnomad4 AMR exome

AF:

0.442

Gnomad4 ASJ exome

AF:

0.239

Gnomad4 EAS exome

AF:

0.473

Gnomad4 SAS exome

AF:

0.405

Gnomad4 FIN exome

AF:

0.304

Gnomad4 NFE exome

AF:

0.318

Gnomad4 OTH exome

AF:

0.304

GnomAD4 genome

AF:

0.271

AC:

41202

AN:

152162

Hom.:

6419

Cov.:

AF XY:

0.274

AC XY:

20403

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.131

Gnomad4 AMR

AF:

0.344

Gnomad4 ASJ

AF:

0.240

Gnomad4 EAS

AF:

0.440

Gnomad4 SAS

AF:

0.405

Gnomad4 FIN

AF:

0.299

Gnomad4 NFE

AF:

0.315

Gnomad4 OTH

AF:

0.271

Alfa

AF:

0.291

Hom.:

8385

Bravo

AF:

0.268

Asia WGS

AF:

0.404

AC:

1405

AN:

3478

EpiCase

AF:

0.300

EpiControl

AF:

0.296

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.87

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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