rs8177272

Variant names:

• chr3-133764026-G-A
• rs8177272
• NM_001063.4:c.1204-156G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-133764026-G-A
• chr3-133764026-G-T

Variant summary

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

The NM_001063.4(TF):​c.1204-156G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,166 control chromosomes in the GnomAD database, including 7,282 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 0.29 (7282 hom., cov: 33)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.963
• Publications: 14 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4	c.1204-156G>A		intron_variant	Intron 9 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.1072-156G>A		intron_variant	Intron 15 of 22		NP_001341632.2
TF	NM_001354704.2	c.823-156G>A		intron_variant	Intron 8 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.1204-156G>A		intron_variant	Intron 9 of 16	1	NM_001063.4	ENSP00000385834.3

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44663 AN: 152050 Hom.: 7277 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.294 AC: 44693 AN: 152166 Hom.: 7282 Cov.: 33 AF XY: 0.296 AC XY: 22013 AN XY: 74384

African (AFR) AF: 0.164 AC: 6821 AN: 41558

American (AMR) AF: 0.379 AC: 5793 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 984 AN: 3468

East Asian (EAS) AF: 0.420 AC: 2171 AN: 5174

South Asian (SAS) AF: 0.423 AC: 2039 AN: 4822

European-Finnish (FIN) AF: 0.288 AC: 3045 AN: 10584

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22848 AN: 67972

Other (OTH) AF: 0.303 AC: 639 AN: 2110

Alfa AF: 0.231 Hom.: 1366

Bravo AF: 0.294

Asia WGS AF: 0.389 AC: 1353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.57
PhyloP100		-0.96
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: rs8177272; hg19: chr3-133482870; COSMIC: COSV53918910; COSMIC: COSV53918910;