NM_001063.4:c.325+228C>A

Variant names:

• chr3-133753931-C-A
• rs3811655
• NM_001063.4:c.325+228C>A

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.325+228C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 463,332 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.566
• Publications: 0 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

ENSG00000291042 (HGNC:):

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=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4	c.325+228C>A		intron_variant	Intron 3 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.193+228C>A		intron_variant	Intron 9 of 22		NP_001341632.2
TF	NM_001354704.2	c.-57+228C>A		intron_variant	Intron 2 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.325+228C>A		intron_variant	Intron 3 of 16	1	NM_001063.4	ENSP00000385834.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000216 AC: 1 AN: 463332 Hom.: 0 Cov.: 2 AF XY: 0.00000405 AC XY: 1 AN XY: 246968

African (AFR) AF: 0.00 AC: 0 AN: 12936

American (AMR) AF: 0.00 AC: 0 AN: 23138

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14484

East Asian (EAS) AF: 0.00 AC: 0 AN: 30844

South Asian (SAS) AF: 0.0000209 AC: 1 AN: 47736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1992

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 276676

Other (OTH) AF: 0.00 AC: 0 AN: 26456

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.57
DANN	Benign	0.32
PhyloP100		-0.57

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: rs3811655; hg19: chr3-133472775;