3-133692634-T-C

Variant names:

• chr3-133692634-T-C
• rs1006097
• NM_001354703.2:c.-940+4270T>C

Variant summary

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

The NM_001354703.2(TF):​c.-940+4270T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 151,728 control chromosomes in the GnomAD database, including 19,507 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 0.50 (19497 hom., cov: 31)
  • Exomes 𝑓: 0.50 (10 hom.)
• Consequence: TF NM_001354703.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• 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]

ENSG00000291042 (HGNC:):

INHCAP (HGNC:11759): (inhibitor of carbonic anhydrase pseudogene)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 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.-940+4270T>C		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.209+4270T>C		intron	N/A
	INHCAP	ENST00000475455.1	TSL:6	n.283-140T>C		intron	N/A
	ENSG00000291042	ENST00000490470.5	TSL:4	n.209+4270T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75786 AN: 151542 Hom.: 19466 Cov.: 31

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.479

GnomAD4 exome AF: 0.500 AC: 33 AN: 66 Hom.: 10 AF XY: 0.571 AC XY: 24 AN XY: 42

African (AFR) AF: 1.00 AC: 6 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

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: 0.429 AC: 24 AN: 56

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.500 AC: 75874 AN: 151662 Hom.: 19497 Cov.: 31 AF XY: 0.503 AC XY: 37253 AN XY: 74126

African (AFR) AF: 0.617 AC: 25512 AN: 41354

American (AMR) AF: 0.490 AC: 7478 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1413 AN: 3462

East Asian (EAS) AF: 0.500 AC: 2570 AN: 5136

South Asian (SAS) AF: 0.430 AC: 2061 AN: 4790

European-Finnish (FIN) AF: 0.506 AC: 5325 AN: 10524

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.444 AC: 30093 AN: 67840

Other (OTH) AF: 0.480 AC: 1011 AN: 2106

Alfa AF: 0.459 Hom.: 19008

Bravo AF: 0.505

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.4
DANN	Benign	0.88
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs1006097; hg19: chr3-133411478;