rs7638018

Variant names:

• chr3-133776617-A-G
• rs7638018
• NM_001063.4:c.1873-432A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-133776617-A-G
• chr3-133776617-A-T

Variant summary

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

The NM_001063.4(TF):​c.1873-432A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,106 control chromosomes in the GnomAD database, including 7,436 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 0.30 (7436 hom., cov: 32)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.68
• 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=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4	c.1873-432A>G		intron_variant	Intron 15 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.1741-432A>G		intron_variant	Intron 21 of 22		NP_001341632.2
TF	NM_001354704.2	c.1492-432A>G		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.1873-432A>G		intron_variant	Intron 15 of 16	1	NM_001063.4	ENSP00000385834.3
TF	ENST00000467842.1	n.2867-432A>G		intron_variant	Intron 1 of 1	1
TF	ENST00000461695.1	n.*173-432A>G		intron_variant	Intron 5 of 6	3		ENSP00000419714.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45491 AN: 151988 Hom.: 7431 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.299 AC: 45521 AN: 152106 Hom.: 7436 Cov.: 32 AF XY: 0.301 AC XY: 22362 AN XY: 74348

African (AFR) AF: 0.185 AC: 7666 AN: 41494

American (AMR) AF: 0.380 AC: 5814 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 985 AN: 3466

East Asian (EAS) AF: 0.416 AC: 2154 AN: 5178

South Asian (SAS) AF: 0.423 AC: 2035 AN: 4812

European-Finnish (FIN) AF: 0.286 AC: 3029 AN: 10584

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.336 AC: 22831 AN: 67974

Other (OTH) AF: 0.307 AC: 650 AN: 2114

Alfa AF: 0.284 Hom.: 1965

Bravo AF: 0.301

Asia WGS AF: 0.394 AC: 1370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	15
DANN	Benign	0.85
PhyloP100		2.7
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: rs7638018; hg19: chr3-133495461; COSMIC: COSV53919015;