rs2715627

Variant names:

• chr3-133776005-T-C
• rs2715627
• NM_001063.4:c.1872+388T>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+388T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,136 control chromosomes in the GnomAD database, including 4,678 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 0.24 (4678 hom., cov: 32)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440
• Publications: 6 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+388T>C		intron_variant	Intron 15 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.1740+388T>C		intron_variant	Intron 21 of 22		NP_001341632.2
TF	NM_001354704.2	c.1491+388T>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+388T>C		intron_variant	Intron 15 of 16	1	NM_001063.4	ENSP00000385834.3
TF	ENST00000467842.1	n.2866+388T>C		intron_variant	Intron 1 of 1	1
TF	ENST00000461695.1	n.*172+388T>C		intron_variant	Intron 5 of 6	3		ENSP00000419714.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36697 AN: 152018 Hom.: 4674 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0681

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.241 AC: 36707 AN: 152136 Hom.: 4678 Cov.: 32 AF XY: 0.239 AC XY: 17782 AN XY: 74374

African (AFR) AF: 0.248 AC: 10288 AN: 41496

American (AMR) AF: 0.186 AC: 2838 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 809 AN: 3468

East Asian (EAS) AF: 0.0683 AC: 354 AN: 5184

South Asian (SAS) AF: 0.141 AC: 680 AN: 4820

European-Finnish (FIN) AF: 0.316 AC: 3345 AN: 10570

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17449 AN: 67992

Other (OTH) AF: 0.237 AC: 502 AN: 2114

Alfa AF: 0.234 Hom.: 1721

Bravo AF: 0.233

Asia WGS AF: 0.129 AC: 450 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	1.6
DANN	Benign	0.60
PhyloP100		-0.44
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: rs2715627; hg19: chr3-133494849;