rs8177185

Variant names:

• chr3-133745774-G-A
• rs8177185
• NM_001354703.2:c.-89-2638G>A

Variant summary

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

The NM_001354703.2(TF):​c.-89-2638G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0824 in 152,220 control chromosomes in the GnomAD database, including 696 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 0.082 (696 hom., cov: 33)
• Consequence: TF NM_001354703.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275
• Publications: 4 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

ENSG00000291042 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) 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_001354703.2	c.-89-2638G>A		intron_variant	Intron 7 of 22		NP_001341632.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000291042	ENST00000460564.5	n.382-7821G>A		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.0823 AC: 12521 AN: 152100 Hom.: 691 Cov.: 33

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0622

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0210

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0515

Gnomad OTH AF: 0.0879

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

GnomAD4 genome AF: 0.0824 AC: 12540 AN: 152220 Hom.: 696 Cov.: 33 AF XY: 0.0829 AC XY: 6172 AN XY: 74424

African (AFR) AF: 0.115 AC: 4761 AN: 41520

American (AMR) AF: 0.106 AC: 1628 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0622 AC: 216 AN: 3472

East Asian (EAS) AF: 0.265 AC: 1369 AN: 5164

South Asian (SAS) AF: 0.128 AC: 619 AN: 4824

European-Finnish (FIN) AF: 0.0210 AC: 223 AN: 10620

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0515 AC: 3502 AN: 68002

Other (OTH) AF: 0.0903 AC: 191 AN: 2116

Alfa AF: 0.0636 Hom.: 443

Bravo AF: 0.0910

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.67
PhyloP100		0.28
PromoterAI		0.14	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8177185; hg19: chr3-133464618;