rs1115219

Variant names:

• chr3-133776173-T-C
• rs1115219
• NM_001063.4:c.1872+556T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001063.4(TF):​c.1872+556T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,192 control chromosomes in the GnomAD database, including 4,138 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 (4138 hom., cov: 32)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• atransferrinemia

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4	c.1872+556T>C		intron_variant	Intron 15 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.1740+556T>C		intron_variant	Intron 21 of 22		NP_001341632.2
TF	NM_001354704.2	c.1491+556T>C		intron_variant	Intron 14 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.1872+556T>C		intron_variant	Intron 15 of 16	1	NM_001063.4	ENSP00000385834.3
TF	ENST00000467842.1	n.2866+556T>C		intron_variant	Intron 1 of 1	1
TF	ENST00000461695.1	n.*172+556T>C		intron_variant	Intron 5 of 6	3		ENSP00000419714.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34420 AN: 152072 Hom.: 4136 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0677

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.226 AC: 34421 AN: 152192 Hom.: 4138 Cov.: 32 AF XY: 0.224 AC XY: 16695 AN XY: 74414

African (AFR) AF: 0.195 AC: 8115 AN: 41534

American (AMR) AF: 0.180 AC: 2751 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 810 AN: 3468

East Asian (EAS) AF: 0.0679 AC: 352 AN: 5186

South Asian (SAS) AF: 0.141 AC: 680 AN: 4818

European-Finnish (FIN) AF: 0.316 AC: 3352 AN: 10592

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17441 AN: 67988

Other (OTH) AF: 0.226 AC: 477 AN: 2108

Alfa AF: 0.240 Hom.: 3440

Bravo AF: 0.215

Asia WGS AF: 0.125 AC: 435 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	3.2
DANN	Benign	0.28
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1115219; hg19: chr3-133495017;