chr3-133703660-A-G

Variant names:

• chr3-133703660-A-G
• rs6769437
• NM_001354703.2:c.-768+2607A>G

Variant summary

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

The NM_001354703.2(TF):​c.-768+2607A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 152,054 control chromosomes in the GnomAD database, including 42,853 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 0.75 (42853 hom., cov: 32)
• Consequence: TF NM_001354703.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161
• Publications: 1 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]

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

ENSG00000291042 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.809 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.-768+2607A>G		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.381+2607A>G		intron	N/A
	INHCAP	ENST00000475455.1	TSL:6	n.1180-564A>G		intron	N/A
	ENSG00000291042	ENST00000490470.5	TSL:4	n.381+2607A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113441 AN: 151936 Hom.: 42828 Cov.: 32

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.747 AC: 113510 AN: 152054 Hom.: 42853 Cov.: 32 AF XY: 0.741 AC XY: 55046 AN XY: 74330

African (AFR) AF: 0.659 AC: 27283 AN: 41430

American (AMR) AF: 0.758 AC: 11578 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 2798 AN: 3472

East Asian (EAS) AF: 0.550 AC: 2845 AN: 5174

South Asian (SAS) AF: 0.697 AC: 3362 AN: 4824

European-Finnish (FIN) AF: 0.747 AC: 7889 AN: 10558

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.815 AC: 55415 AN: 68004

Other (OTH) AF: 0.741 AC: 1563 AN: 2110

Alfa AF: 0.796 Hom.: 21713

Bravo AF: 0.742

Asia WGS AF: 0.591 AC: 2055 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.80
PhyloP100		-0.16

Splicing

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

Other links and lift over

dbSNP: rs6769437; hg19: chr3-133422504;