rs3811655

chr3-133753931-C-Gchr3-133753931-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.325+228C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 614,792 control chromosomes in the GnomAD database, including 20,063 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 0.23 (4339 hom., cov: 32)
  • Exomes 𝑓: 0.26 (15724 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.566

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]

(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 (NFE) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TF	NM_001063.4	c.325+228C>G		intron_variant		ENST00000402696.9
TF	NM_001354703.2	c.193+228C>G		intron_variant
TF	NM_001354704.2	c.-57+228C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TF	ENST00000402696.9	c.325+228C>G		intron_variant		1	NM_001063.4	P1
	ENST00000460564.5	n.490+228C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35325 AN: 151758 Hom.: 4335 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.257 AC: 118773 AN: 462916 Hom.: 15724 Cov.: 2 AF XY: 0.255 AC XY: 62801 AN XY: 246716

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.240

Gnomad4 ASJ exome AF: 0.324

Gnomad4 EAS exome AF: 0.224

Gnomad4 SAS exome AF: 0.194

Gnomad4 FIN exome AF: 0.211

Gnomad4 NFE exome AF: 0.278

Gnomad4 OTH exome AF: 0.255

GnomAD4 genome AF: 0.233 AC: 35356 AN: 151876 Hom.: 4339 Cov.: 32 AF XY: 0.231 AC XY: 17134 AN XY: 74192

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.231

Alfa AF: 0.248 Hom.: 668

Bravo AF: 0.232

Asia WGS AF: 0.198 AC: 691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.57
Dann	Benign	0.64

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: rs3811655; hg19: chr3-133472775;