chr3-133749295-G-A

Variant names:

• chr3-133749295-G-A
• rs8177191
• NM_001063.4:c.216+711G>A

Variant summary

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

The NM_001063.4(TF):​c.216+711G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,180 control chromosomes in the GnomAD database, including 1,490 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 0.13 (1490 hom., cov: 32)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.938
• Publications: 11 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, MODERATE, SUPPORTIVE, LIMITED Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.185 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	NM_001063.4	MANE Select	c.216+711G>A		intron	N/A	NP_001054.2	P02787
	TF	NM_001354703.2		c.84+711G>A		intron	N/A	NP_001341632.2
	TF	NM_001354704.2		c.-166+2812G>A		intron	N/A	NP_001341633.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	ENST00000402696.9	TSL:1 MANE Select	c.216+711G>A		intron	N/A	ENSP00000385834.3	P02787
	TF	ENST00000877249.1		c.43+2812G>A		intron	N/A	ENSP00000547308.1
	TF	ENST00000877246.1		c.216+711G>A		intron	N/A	ENSP00000547305.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20375 AN: 152062 Hom.: 1489 Cov.: 32

Gnomad AFR AF: 0.0808

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.0998

Gnomad FIN AF: 0.0905

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.149

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.134 AC: 20384 AN: 152180 Hom.: 1490 Cov.: 32 AF XY: 0.132 AC XY: 9820 AN XY: 74414

African (AFR) AF: 0.0807 AC: 3351 AN: 41530

American (AMR) AF: 0.138 AC: 2107 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 674 AN: 3470

East Asian (EAS) AF: 0.195 AC: 1005 AN: 5166

South Asian (SAS) AF: 0.101 AC: 488 AN: 4818

European-Finnish (FIN) AF: 0.0905 AC: 960 AN: 10602

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11265 AN: 67986

Other (OTH) AF: 0.147 AC: 311 AN: 2110

Alfa AF: 0.160 Hom.: 8649

Bravo AF: 0.136

Asia WGS AF: 0.126 AC: 439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.7
DANN	Benign	0.49
PhyloP100		0.94
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: rs8177191; hg19: chr3-133468139;