3-133756770-G-C

Variant names:

• chr3-133756770-G-C
• rs7633232
• NM_001063.4:c.692-61G>C

Variant summary

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

The NM_001063.4(TF):​c.692-61G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 1,594,456 control chromosomes in the GnomAD database, including 116 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 0.015 (53 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (63 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0515 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	NM_001063.4	MANE Select	c.692-61G>C		intron	N/A	NP_001054.2
	TF	NM_001354703.2		c.560-61G>C		intron	N/A	NP_001341632.2
	TF	NM_001354704.2		c.311-61G>C		intron	N/A	NP_001341633.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	ENST00000402696.9	TSL:1 MANE Select	c.692-61G>C		intron	N/A	ENSP00000385834.3
	TF	ENST00000482271.5	TSL:4	c.311-61G>C		intron	N/A	ENSP00000419338.1
	TF	ENST00000485977.1	TSL:3	n.158-162G>C		intron	N/A	ENSP00000418716.1

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2332 AN: 152126 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.0532

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00615

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.00161 AC: 2318 AN: 1442212 Hom.: 63 AF XY: 0.00136 AC XY: 976 AN XY: 718566

African (AFR) AF: 0.0566 AC: 1869 AN: 33018

American (AMR) AF: 0.00336 AC: 150 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26010

East Asian (EAS) AF: 0.00 AC: 0 AN: 39596

South Asian (SAS) AF: 0.000175 AC: 15 AN: 85816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53198

Middle Eastern (MID) AF: 0.000926 AC: 5 AN: 5402

European-Non Finnish (NFE) AF: 0.0000804 AC: 88 AN: 1094718

Other (OTH) AF: 0.00320 AC: 191 AN: 59758

GnomAD4 genome AF: 0.0154 AC: 2342 AN: 152244 Hom.: 53 Cov.: 32 AF XY: 0.0151 AC XY: 1124 AN XY: 74428

African (AFR) AF: 0.0533 AC: 2215 AN: 41550

American (AMR) AF: 0.00608 AC: 93 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68008

Other (OTH) AF: 0.0128 AC: 27 AN: 2110

Alfa AF: 0.000774 Hom.: 0

Bravo AF: 0.0177

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.0
DANN	Benign	0.51
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7633232; hg19: chr3-133475614;