chr3-133755763-G-C

Variant names:

• chr3-133755763-G-C
• rs3811657
• NM_001063.4:c.635+268G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001063.4(TF):​c.635+268G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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.635+268G>C		intron	N/A	NP_001054.2
	TF	NM_001354703.2		c.503+268G>C		intron	N/A	NP_001341632.2
	TF	NM_001354704.2		c.254+268G>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.635+268G>C		intron	N/A	ENSP00000385834.3
	TF	ENST00000493011.5	TSL:2	n.951G>C		non_coding_transcript_exon	Exon 5 of 5
	TF	ENST00000482271.5	TSL:4	c.254+268G>C		intron	N/A	ENSP00000419338.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 384942 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 204724

African (AFR) AF: 0.00 AC: 0 AN: 11074

American (AMR) AF: 0.00 AC: 0 AN: 16350

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11536

East Asian (EAS) AF: 0.00 AC: 0 AN: 24320

South Asian (SAS) AF: 0.00 AC: 0 AN: 44862

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1614

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 230372

Other (OTH) AF: 0.00 AC: 0 AN: 22010

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.042
DANN	Benign	0.46
PhyloP100		-0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3811657; hg19: chr3-133474607;