rs8177252

Positions:

• chr3-133761330-C-A
• chr3-133761330-C-G
• chr3-133761330-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+2001C>A 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 158,634 control chromosomes in the GnomAD database, including 8,333 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 (7901 hom., cov: 31)
  • Exomes 𝑓: 0.35 (432 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19

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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TF	NM_001063.4	c.1203+2001C>A		intron_variant		ENST00000402696.9
TF	NM_001354703.2	c.1071+2001C>A		intron_variant
TF	NM_001354704.2	c.822+2001C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TF	ENST00000402696.9	c.1203+2001C>A		intron_variant		1	NM_001063.4	P1
ACSL3P1	ENST00000474389.1	n.1031C>A		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47914 AN: 151654 Hom.: 7889 Cov.: 31

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.318

GnomAD4 exome AF: 0.345 AC: 2370 AN: 6862 Hom.: 432 Cov.: 0 AF XY: 0.340 AC XY: 1452 AN XY: 4274

Gnomad4 AFR exome AF: 0.209

Gnomad4 AMR exome AF: 0.509

Gnomad4 ASJ exome AF: 0.257

Gnomad4 EAS exome AF: 0.414

Gnomad4 SAS exome AF: 0.425

Gnomad4 FIN exome AF: 0.308

Gnomad4 NFE exome AF: 0.311

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.316 AC: 47968 AN: 151772 Hom.: 7901 Cov.: 31 AF XY: 0.318 AC XY: 23545 AN XY: 74140

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.320

Alfa AF: 0.230 Hom.: 646

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	-0.71
CADD	Benign	1.2
DANN	Benign	0.56
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: rs8177252; hg19: chr3-133480174;