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

Variant names:

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

Variant summary

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

The NM_001063.4(TF):​c.325+228C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 614,792 control chromosomes in the GnomAD database, including 20,063 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 0.23 (4339 hom., cov: 32)
  • Exomes 𝑓: 0.26 (15724 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.566
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.273 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.325+228C>G		intron	N/A	NP_001054.2
	TF	NM_001354703.2		c.193+228C>G		intron	N/A	NP_001341632.2
	TF	NM_001354704.2		c.-57+228C>G		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.325+228C>G		intron	N/A	ENSP00000385834.3
	TF	ENST00000460531.5	TSL:4	n.428C>G		non_coding_transcript_exon	Exon 2 of 2
	TF	ENST00000482271.5	TSL:4	c.-57+228C>G		intron	N/A	ENSP00000419338.1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35325 AN: 151758 Hom.: 4335 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.257 AC: 118773 AN: 462916 Hom.: 15724 Cov.: 2 AF XY: 0.255 AC XY: 62801 AN XY: 246716

African (AFR) AF: 0.168 AC: 2170 AN: 12924

American (AMR) AF: 0.240 AC: 5547 AN: 23116

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 4689 AN: 14466

East Asian (EAS) AF: 0.224 AC: 6912 AN: 30804

South Asian (SAS) AF: 0.194 AC: 9281 AN: 47728

European-Finnish (FIN) AF: 0.211 AC: 6120 AN: 29042

Middle Eastern (MID) AF: 0.262 AC: 521 AN: 1992

European-Non Finnish (NFE) AF: 0.278 AC: 76792 AN: 276418

Other (OTH) AF: 0.255 AC: 6741 AN: 26426

GnomAD4 genome AF: 0.233 AC: 35356 AN: 151876 Hom.: 4339 Cov.: 32 AF XY: 0.231 AC XY: 17134 AN XY: 74192

African (AFR) AF: 0.160 AC: 6624 AN: 41416

American (AMR) AF: 0.245 AC: 3746 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1143 AN: 3470

East Asian (EAS) AF: 0.228 AC: 1167 AN: 5120

South Asian (SAS) AF: 0.190 AC: 914 AN: 4810

European-Finnish (FIN) AF: 0.204 AC: 2156 AN: 10556

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.277 AC: 18799 AN: 67920

Other (OTH) AF: 0.231 AC: 487 AN: 2106

Alfa AF: 0.248 Hom.: 668

Bravo AF: 0.232

Asia WGS AF: 0.198 AC: 691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.57
DANN	Benign	0.64
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism (auto)

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;