chr3-133779945-G-A

Variant names:

• chr3-133779945-G-A
• rs4854761
• NM_001063.4:c.*1325G>A

Variant summary

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

The NM_001063.4(TF):​c.*1325G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,982 control chromosomes in the GnomAD database, including 8,536 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 0.33 (8536 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TF NM_001063.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001063.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	NM_001063.4	MANE Select	c.*1325G>A		3_prime_UTR	Exon 17 of 17	NP_001054.2
	TF	NM_001354703.2		c.*1325G>A		3_prime_UTR	Exon 23 of 23	NP_001341632.2
	TF	NM_001354704.2		c.*1325G>A		3_prime_UTR	Exon 16 of 16	NP_001341633.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	ENST00000402696.9	TSL:1 MANE Select	c.*1325G>A		3_prime_UTR	Exon 17 of 17	ENSP00000385834.3

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50032 AN: 151864 Hom.: 8528 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.325

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 8

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.329 AC: 50074 AN: 151982 Hom.: 8536 Cov.: 32 AF XY: 0.329 AC XY: 24465 AN XY: 74278

African (AFR) AF: 0.293 AC: 12133 AN: 41440

American (AMR) AF: 0.391 AC: 5968 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 939 AN: 3468

East Asian (EAS) AF: 0.418 AC: 2161 AN: 5170

South Asian (SAS) AF: 0.423 AC: 2029 AN: 4798

European-Finnish (FIN) AF: 0.278 AC: 2934 AN: 10570

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22864 AN: 67958

Other (OTH) AF: 0.326 AC: 689 AN: 2112

Alfa AF: 0.327 Hom.: 2577

Bravo AF: 0.335

Asia WGS AF: 0.398 AC: 1382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.52
DANN	Benign	0.55
PhyloP100		-0.36

Splicing

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

Other links and lift over

dbSNP: rs4854761; hg19: chr3-133498789;