rs8177326

Positions:

• chr3-133762372-C-A

Variant summary

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

The NM_001063.4(TF):​c.1204-1810C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0328 in 153,506 control chromosomes in the GnomAD database, including 223 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 0.033 (222 hom., cov: 32)
  • Exomes 𝑓: 0.039 (1 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.544

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TF	NM_001063.4	c.1204-1810C>A		intron_variant		ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.1072-1810C>A		intron_variant			NP_001341632.2
TF	NM_001354704.2	c.823-1810C>A		intron_variant			NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.1204-1810C>A		intron_variant		1	NM_001063.4	ENSP00000385834	P1
ACSL3P1	ENST00000474389.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0326 AC: 4960 AN: 152092 Hom.: 214 Cov.: 32

Gnomad AFR AF: 0.00674

Gnomad AMI AF: 0.0473

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.0323

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0342

Gnomad OTH AF: 0.0388

GnomAD4 exome AF: 0.0386 AC: 50 AN: 1296 Hom.: 1 Cov.: 0 AF XY: 0.0332 AC XY: 26 AN XY: 784

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.106

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00424

Gnomad4 FIN exome AF: 0.0495

Gnomad4 NFE exome AF: 0.0349

Gnomad4 OTH exome AF: 0.0814

GnomAD4 genome AF: 0.0327 AC: 4978 AN: 152210 Hom.: 222 Cov.: 32 AF XY: 0.0325 AC XY: 2420 AN XY: 74422

Gnomad4 AFR AF: 0.00672

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0499

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.0145

Gnomad4 FIN AF: 0.0323

Gnomad4 NFE AF: 0.0341

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0426 Hom.: 26

Bravo AF: 0.0399

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.44

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: rs8177326; hg19: chr3-133481216;