rs2715631

Variant names:

• chr3-133764045-T-G
• rs2715631
• NM_001063.4:c.1204-137T>G

Variant summary

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

The NM_001063.4(TF):​c.1204-137T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 744,354 control chromosomes in the GnomAD database, including 19,345 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 0.20 (3506 hom., cov: 33)
  • Exomes 𝑓: 0.22 (15839 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 9 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4	c.1204-137T>G		intron_variant	Intron 9 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.1072-137T>G		intron_variant	Intron 15 of 22		NP_001341632.2
TF	NM_001354704.2	c.823-137T>G		intron_variant	Intron 8 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.1204-137T>G		intron_variant	Intron 9 of 16	1	NM_001063.4	ENSP00000385834.3

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30387 AN: 152104 Hom.: 3505 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0677

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.221 AC: 130579 AN: 592132 Hom.: 15839 AF XY: 0.218 AC XY: 69907 AN XY: 320978

African (AFR) AF: 0.104 AC: 1769 AN: 16976

American (AMR) AF: 0.129 AC: 4856 AN: 37740

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 4541 AN: 19428

East Asian (EAS) AF: 0.0811 AC: 2726 AN: 33614

South Asian (SAS) AF: 0.146 AC: 9622 AN: 66030

European-Finnish (FIN) AF: 0.307 AC: 13352 AN: 43560

Middle Eastern (MID) AF: 0.255 AC: 643 AN: 2518

European-Non Finnish (NFE) AF: 0.252 AC: 86103 AN: 341340

Other (OTH) AF: 0.225 AC: 6967 AN: 30926

GnomAD4 genome AF: 0.199 AC: 30368 AN: 152222 Hom.: 3506 Cov.: 33 AF XY: 0.199 AC XY: 14798 AN XY: 74410

African (AFR) AF: 0.104 AC: 4334 AN: 41540

American (AMR) AF: 0.170 AC: 2595 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 810 AN: 3470

East Asian (EAS) AF: 0.0678 AC: 352 AN: 5188

South Asian (SAS) AF: 0.142 AC: 685 AN: 4834

European-Finnish (FIN) AF: 0.319 AC: 3371 AN: 10572

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17335 AN: 68000

Other (OTH) AF: 0.210 AC: 444 AN: 2114

Alfa AF: 0.220 Hom.: 1641

Bravo AF: 0.185

Asia WGS AF: 0.124 AC: 430 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	0.087
DANN	Benign	0.72
PhyloP100		-1.4
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: rs2715631; hg19: chr3-133482889;