3-133746357-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000460564.5(ENSG00000291042):n.382-7238G>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0643 in 1,500,568 control chromosomes in the GnomAD database, including 4,586 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.082 (697 hom., cov: 33)
  • Exomes 𝑓: 0.062 (3889 hom.)
• Consequence: ENST00000460564.5 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-133746357-G-T is Benign according to our data. Variant chr3-133746357-G-T is described in ClinVar as [Benign]. Clinvar id is 343420.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TF	NM_001354703.2	c.-89-2055G>T		intron_variant
TF	NM_001063.4			upstream_gene_variant		ENST00000402696.9
TF	NM_001354704.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000460564.5	n.382-7238G>T		intron_variant, non_coding_transcript_variant		4
TF	ENST00000402696.9			upstream_gene_variant		1	NM_001063.4	P1

Frequencies

GnomAD3 genomes AF: 0.0821 AC: 12486 AN: 152166 Hom.: 692 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0207

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.0509

Gnomad OTH AF: 0.0870

GnomAD4 exome AF: 0.0623 AC: 84002 AN: 1348282 Hom.: 3889 Cov.: 23 AF XY: 0.0637 AC XY: 42511 AN XY: 667740

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.0650

Gnomad4 EAS exome AF: 0.239

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.0205

Gnomad4 NFE exome AF: 0.0502

Gnomad4 OTH exome AF: 0.0790

GnomAD4 genome AF: 0.0821 AC: 12506 AN: 152286 Hom.: 697 Cov.: 33 AF XY: 0.0828 AC XY: 6165 AN XY: 74460

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0617

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.0207

Gnomad4 NFE AF: 0.0509

Gnomad4 OTH AF: 0.0894

Alfa AF: 0.0300 Hom.: 30

Bravo AF: 0.0908

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Atransferrinemia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 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	-0.80
Cadd	Benign	5.0
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs8177186; hg19: chr3-133465201; COSMIC: COSV53923722; COSMIC: COSV53923722;