rs8177262

Positions:

• chr3-133761808-G-A
• chr3-133761808-G-C

Variant summary

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

The ENST00000402696.9(TF):​c.1204-2374G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,940 control chromosomes in the GnomAD database, including 7,877 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 0.31 (7829 hom., cov: 33)
  • Exomes 𝑓: 0.33 (48 hom.)
• Consequence: TF ENST00000402696.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

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 (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.1204-2374G>A		intron_variant		ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.1072-2374G>A		intron_variant			NP_001341632.2
TF	NM_001354704.2	c.823-2374G>A		intron_variant			NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.1204-2374G>A		intron_variant		1	NM_001063.4	ENSP00000385834	P1
ACSL3P1	ENST00000474389.1	n.1362G>A		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47400 AN: 151982 Hom.: 7818 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.315

GnomAD4 exome AF: 0.326 AC: 274 AN: 840 Hom.: 48 Cov.: 0 AF XY: 0.318 AC XY: 149 AN XY: 468

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.450

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 0.278

Gnomad4 SAS exome AF: 0.875

Gnomad4 FIN exome AF: 0.308

Gnomad4 NFE exome AF: 0.330

Gnomad4 OTH exome AF: 0.462

GnomAD4 genome AF: 0.312 AC: 47450 AN: 152100 Hom.: 7829 Cov.: 33 AF XY: 0.313 AC XY: 23303 AN XY: 74362

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.316

Alfa AF: 0.330 Hom.: 1599

Bravo AF: 0.315

Asia WGS AF: 0.402 AC: 1397 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	0.48
DANN	Benign	0.79

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: rs8177262; hg19: chr3-133480652; COSMIC: COSV53918871; COSMIC: COSV53918871;