chr3-133768777-C-G

Position:

• chr3-133768777-C-G

Variant summary

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

The ENST00000402696.9(TF):​c.1622+613C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 146,002 control chromosomes in the GnomAD database, including 5,077 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 0.26 (5077 hom., cov: 28)
• Consequence: TF ENST00000402696.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TF	NM_001063.4	c.1622+613C>G		intron_variant		ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.1490+613C>G		intron_variant			NP_001341632.2
TF	NM_001354704.2	c.1241+613C>G		intron_variant			NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.1622+613C>G		intron_variant		1	NM_001063.4	ENSP00000385834	P1
TF	ENST00000461695.1	c.292+613C>G		intron_variant, NMD_transcript_variant		3		ENSP00000419714
TF	ENST00000462495.1	n.133+613C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.255 AC: 37231 AN: 145938 Hom.: 5076 Cov.: 28

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0660

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.284

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.254

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.255 AC: 37235 AN: 146002 Hom.: 5077 Cov.: 28 AF XY: 0.250 AC XY: 17587 AN XY: 70368

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.0662

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.251

Alfa AF: 0.243 Hom.: 652

Bravo AF: 0.252

Asia WGS AF: 0.132 AC: 461 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.1
DANN	Benign	0.73

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: rs1358022; hg19: chr3-133487621;