rs8649

Positions:

Variant summary

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

The NM_001063.4(TF):c.1572G>C(p.Leu524Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,613,778 control chromosomes in the GnomAD database, including 50,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5361 hom., cov: 32)

Exomes 𝑓: 0.24 ( 45250 hom. )

Consequence

TF
NM_001063.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.621

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:

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=-0.65).

BP6

Variant 3-133768114-G-C is Benign according to our data. Variant chr3-133768114-G-C is described in ClinVar as [Benign]. Clinvar id is 343444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-133768114-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.621 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 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.1572G>C	p.Leu524Leu	synonymous_variant	13/17	ENST00000402696.9	NP_001054.2	P02787Q06AH7A0PJA6
TF	NM_001354703.2 linkuse as main transcript	c.1440G>C	p.Leu480Leu	synonymous_variant	19/23		NP_001341632.2
TF	NM_001354704.2 linkuse as main transcript	c.1191G>C	p.Leu397Leu	synonymous_variant	12/16		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TF	ENST00000402696.9 linkuse as main transcript	c.1572G>C	p.Leu524Leu	synonymous_variant	13/17	1	NM_001063.4	ENSP00000385834.3	P02787
TF	ENST00000461695.1 linkuse as main transcript	n.240G>C		non_coding_transcript_exon_variant	2/7	3		ENSP00000419714.1	H7C5E8
TF	ENST00000462495.1 linkuse as main transcript	n.83G>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39277

AN:

151958

Hom.:

5358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.312

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.188

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.0679

Gnomad SAS

AF:

0.142

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.253

GnomAD3 exomes

AF:

0.218

AC:

54896

AN:

251394

Hom.:

6749

AF XY:

0.218

AC XY:

29601

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.310

Gnomad AMR exome

AF:

0.132

Gnomad ASJ exome

AF:

0.236

Gnomad EAS exome

AF:

0.0684

Gnomad SAS exome

AF:

0.149

Gnomad FIN exome

AF:

0.314

Gnomad NFE exome

AF:

0.254

Gnomad OTH exome

AF:

0.238

GnomAD4 exome

AF:

0.243

AC:

355774

AN:

1461702

Hom.:

45250

Cov.:

AF XY:

0.240

AC XY:

174528

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.314

Gnomad4 AMR exome

AF:

0.139

Gnomad4 ASJ exome

AF:

0.234

Gnomad4 EAS exome

AF:

0.0798

Gnomad4 SAS exome

AF:

0.148

Gnomad4 FIN exome

AF:

0.307

Gnomad4 NFE exome

AF:

0.256

Gnomad4 OTH exome

AF:

0.241

GnomAD4 genome

AF:

0.258

AC:

39292

AN:

152076

Hom.:

5361

Cov.:

AF XY:

0.255

AC XY:

18990

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.312

Gnomad4 AMR

AF:

0.188

Gnomad4 ASJ

AF:

0.233

Gnomad4 EAS

AF:

0.0680

Gnomad4 SAS

AF:

0.141

Gnomad4 FIN

AF:

0.316

Gnomad4 NFE

AF:

0.255

Gnomad4 OTH

AF:

0.250

Alfa

AF:

0.229

Hom.:

3190

Bravo

AF:

0.253

Asia WGS

AF:

0.137

AC:

476

AN:

3478

EpiCase

AF:

0.250

EpiControl

AF:

0.250

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Atransferrinemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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

-0.65

CADD

Benign

1.3

DANN

Benign

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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