rs8177253

Positions:

• chr3-133761348-C-T

Variant summary

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

The NM_001063.4(TF):​c.1203+2019C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 154,176 control chromosomes in the GnomAD database, including 8,078 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 0.32 (7922 hom., cov: 32)
  • Exomes 𝑓: 0.37 (156 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.92

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TF	NM_001063.4	c.1203+2019C>T		intron_variant		ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.1071+2019C>T		intron_variant			NP_001341632.2
TF	NM_001354704.2	c.822+2019C>T		intron_variant			NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.1203+2019C>T		intron_variant		1	NM_001063.4	ENSP00000385834	P1
ACSL3P1	ENST00000474389.1	n.1049C>T		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47964 AN: 151710 Hom.: 7910 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.371 AC: 870 AN: 2348 Hom.: 156 Cov.: 0 AF XY: 0.378 AC XY: 565 AN XY: 1496

Gnomad4 AFR exome AF: 0.214

Gnomad4 AMR exome AF: 0.477

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.444

Gnomad4 SAS exome AF: 0.514

Gnomad4 FIN exome AF: 0.327

Gnomad4 NFE exome AF: 0.345

Gnomad4 OTH exome AF: 0.361

GnomAD4 genome AF: 0.316 AC: 48018 AN: 151828 Hom.: 7922 Cov.: 32 AF XY: 0.318 AC XY: 23572 AN XY: 74178

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.320

Alfa AF: 0.333 Hom.: 1624

Bravo AF: 0.320

Asia WGS AF: 0.402 AC: 1399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.62
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs8177253; hg19: chr3-133480192;