rs12595

Positions:

• chr3-133777709-T-C
• chr3-133777709-T-G

Variant summary

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

The NM_001063.4(TF):​c.2062+471T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 173,654 control chromosomes in the GnomAD database, including 8,700 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 0.30 (7410 hom., cov: 33)
  • Exomes 𝑓: 0.32 (1290 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549

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]

TF (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TF	NM_001063.4	c.2062+471T>C		intron_variant		ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.1930+471T>C		intron_variant			NP_001341632.2
TF	NM_001354704.2	c.1681+471T>C		intron_variant			NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.2062+471T>C		intron_variant		1	NM_001063.4	ENSP00000385834.3
TF	ENST00000467842.1	n.3527T>C		non_coding_transcript_exon_variant	2/2	1
TF	ENST00000461695.1	n.*362+471T>C		intron_variant		3		ENSP00000419714.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45446 AN: 152024 Hom.: 7405 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.321 AC: 6904 AN: 21512 Hom.: 1290 Cov.: 0 AF XY: 0.327 AC XY: 3586 AN XY: 10964

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.413

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.354

Gnomad4 SAS exome AF: 0.390

Gnomad4 FIN exome AF: 0.277

Gnomad4 NFE exome AF: 0.295

Gnomad4 OTH exome AF: 0.306

GnomAD4 genome AF: 0.299 AC: 45476 AN: 152142 Hom.: 7410 Cov.: 33 AF XY: 0.300 AC XY: 22348 AN XY: 74374

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.308

Alfa AF: 0.201 Hom.: 529

Bravo AF: 0.300

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.3
DANN	Benign	0.85

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: rs12595; hg19: chr3-133496553; COSMIC: COSV53919024;