rs1405023

chr3-133762284-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001063.4(TF):c.1204-1898T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 180,864 control chromosomes in the GnomAD database, including 20,338 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 0.48 (17963 hom., cov: 32)
  • Exomes 𝑓: 0.40 (2375 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24

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]

ACSL3P1 (HGNC:56529): (ACSL3 pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TF	NM_001063.4	c.1204-1898T>C		intron_variant		ENST00000402696.9
TF	NM_001354703.2	c.1072-1898T>C		intron_variant
TF	NM_001354704.2	c.823-1898T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TF	ENST00000402696.9	c.1204-1898T>C		intron_variant		1	NM_001063.4	P1
ACSL3P1	ENST00000474389.1	n.1838T>C		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72770 AN: 151932 Hom.: 17948 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.485

GnomAD4 exome AF: 0.398 AC: 11476 AN: 28814 Hom.: 2375 Cov.: 0 AF XY: 0.407 AC XY: 6702 AN XY: 16474

Gnomad4 AFR exome AF: 0.598

Gnomad4 AMR exome AF: 0.229

Gnomad4 ASJ exome AF: 0.484

Gnomad4 EAS exome AF: 0.330

Gnomad4 SAS exome AF: 0.359

Gnomad4 FIN exome AF: 0.410

Gnomad4 NFE exome AF: 0.438

Gnomad4 OTH exome AF: 0.454

GnomAD4 genome AF: 0.479 AC: 72819 AN: 152050 Hom.: 17963 Cov.: 32 AF XY: 0.474 AC XY: 35233 AN XY: 74360

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.479

Alfa AF: 0.464 Hom.: 3675

Bravo AF: 0.481

Asia WGS AF: 0.346 AC: 1207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	11
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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

Other links and lift over

dbSNP: rs1405023; hg19: chr3-133481128;