chr3-133754428-C-T

Variant names:

• chr3-133754428-C-T
• rs6778321
• NM_001063.4:c.326-67C>T

Variant summary

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

The ENST00000402696.9(TF):​c.326-67C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00686 in 1,529,140 control chromosomes in the GnomAD database, including 577 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 0.035 (301 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (276 hom.)
• Consequence: TF ENST00000402696.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• 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

ENSG00000291042 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000402696.9. 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.326-67C>T		intron	N/A	NP_001054.2
	TF	NM_001354703.2		c.194-67C>T		intron	N/A	NP_001341632.2
	TF	NM_001354704.2		c.-56-67C>T		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.326-67C>T		intron	N/A	ENSP00000385834.3
	TF	ENST00000482271.5	TSL:4	c.-56-67C>T		intron	N/A	ENSP00000419338.1
	TF	ENST00000466911.5	TSL:4	c.194-67C>T		intron	N/A	ENSP00000417468.1

Frequencies

GnomAD3 genomes AF: 0.0353 AC: 5364 AN: 152060 Hom.: 301 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.0239

GnomAD4 exome AF: 0.00372 AC: 5129 AN: 1376962 Hom.: 276 AF XY: 0.00321 AC XY: 2217 AN XY: 690170

African (AFR) AF: 0.125 AC: 3925 AN: 31486

American (AMR) AF: 0.00762 AC: 340 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.000156 AC: 4 AN: 25584

East Asian (EAS) AF: 0.0000765 AC: 3 AN: 39216

South Asian (SAS) AF: 0.000274 AC: 23 AN: 83870

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53076

Middle Eastern (MID) AF: 0.00534 AC: 28 AN: 5242

European-Non Finnish (NFE) AF: 0.000316 AC: 328 AN: 1036408

Other (OTH) AF: 0.00832 AC: 478 AN: 57480

GnomAD4 genome AF: 0.0352 AC: 5364 AN: 152178 Hom.: 301 Cov.: 32 AF XY: 0.0347 AC XY: 2581 AN XY: 74396

African (AFR) AF: 0.121 AC: 5016 AN: 41488

American (AMR) AF: 0.0164 AC: 251 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.000624 AC: 3 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68012

Other (OTH) AF: 0.0237 AC: 50 AN: 2110

Alfa AF: 0.00905 Hom.: 13

Bravo AF: 0.0402

Asia WGS AF: 0.00577 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.43
PhyloP100		-1.4
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: rs6778321; hg19: chr3-133473272;