rs1405023

Variant names:

• chr3-133762284-T-C
• rs1405023
• NM_001063.4:c.1204-1898T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001063.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	NM_001063.4	MANE Select	c.1204-1898T>C		intron	N/A	NP_001054.2
	TF	NM_001354703.2		c.1072-1898T>C		intron	N/A	NP_001341632.2
	TF	NM_001354704.2		c.823-1898T>C		intron	N/A	NP_001341633.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	ENST00000402696.9	TSL:1 MANE Select	c.1204-1898T>C		intron	N/A	ENSP00000385834.3
	ACSL3P1	ENST00000474389.1	TSL:6	n.1838T>C		non_coding_transcript_exon	Exon 2 of 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

African (AFR) AF: 0.598 AC: 576 AN: 964

American (AMR) AF: 0.229 AC: 930 AN: 4056

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 177 AN: 366

East Asian (EAS) AF: 0.330 AC: 790 AN: 2394

South Asian (SAS) AF: 0.359 AC: 977 AN: 2720

European-Finnish (FIN) AF: 0.410 AC: 1635 AN: 3990

Middle Eastern (MID) AF: 0.501 AC: 761 AN: 1518

European-Non Finnish (NFE) AF: 0.438 AC: 5131 AN: 11708

Other (OTH) AF: 0.454 AC: 499 AN: 1098

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

African (AFR) AF: 0.593 AC: 24580 AN: 41466

American (AMR) AF: 0.384 AC: 5864 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1636 AN: 3470

East Asian (EAS) AF: 0.320 AC: 1655 AN: 5170

South Asian (SAS) AF: 0.369 AC: 1776 AN: 4812

European-Finnish (FIN) AF: 0.445 AC: 4705 AN: 10580

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30890 AN: 67960

Other (OTH) AF: 0.479 AC: 1008 AN: 2106

Alfa AF: 0.459 Hom.: 6445

Bravo AF: 0.481

Asia WGS AF: 0.346 AC: 1207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1405023; hg19: chr3-133481128;