chr3-133745840-G-A

Variant names:

• chr3-133745840-G-A
• rs4481157
• NM_001354703.2:c.-89-2572G>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.-89-2572G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 155,178 control chromosomes in the GnomAD database, including 13,240 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 0.41 (13089 hom., cov: 32)
  • Exomes 𝑓: 0.27 (151 hom.)
• Consequence: TF NM_001354703.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.596
• Publications: 11 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354703.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	NM_001354703.2		c.-89-2572G>A		intron	N/A	NP_001341632.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000291042	ENST00000460564.5	TSL:4	n.382-7755G>A		intron	N/A
	TF	ENST00000466911.5	TSL:4	c.-499G>A		upstream_gene	N/A	ENSP00000417468.1

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62158 AN: 151894 Hom.: 13071 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.370

GnomAD4 exome AF: 0.268 AC: 847 AN: 3166 Hom.: 151 AF XY: 0.268 AC XY: 424 AN XY: 1582

African (AFR) AF: 0.467 AC: 14 AN: 30

American (AMR) AF: 0.293 AC: 153 AN: 522

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 5 AN: 14

East Asian (EAS) AF: 0.400 AC: 40 AN: 100

South Asian (SAS) AF: 0.285 AC: 41 AN: 144

European-Finnish (FIN) AF: 0.271 AC: 19 AN: 70

Middle Eastern (MID) AF: 0.167 AC: 1 AN: 6

European-Non Finnish (NFE) AF: 0.252 AC: 543 AN: 2158

Other (OTH) AF: 0.254 AC: 31 AN: 122

GnomAD4 genome AF: 0.409 AC: 62225 AN: 152012 Hom.: 13089 Cov.: 32 AF XY: 0.412 AC XY: 30571 AN XY: 74284

African (AFR) AF: 0.478 AC: 19832 AN: 41466

American (AMR) AF: 0.417 AC: 6373 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1100 AN: 3472

East Asian (EAS) AF: 0.468 AC: 2410 AN: 5152

South Asian (SAS) AF: 0.526 AC: 2528 AN: 4806

European-Finnish (FIN) AF: 0.385 AC: 4069 AN: 10558

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24818 AN: 67954

Other (OTH) AF: 0.370 AC: 781 AN: 2110

Alfa AF: 0.397 Hom.: 1967

Bravo AF: 0.414

Asia WGS AF: 0.511 AC: 1777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.3
DANN	Benign	0.54
PhyloP100		0.60
PromoterAI		0.027	Neutral

Splicing

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

Other links and lift over

dbSNP: rs4481157; hg19: chr3-133464684;