chr3-133765185-G-A

Variant names:

• chr3-133765185-G-A
• rs3811647
• NM_001063.4:c.1330+278G>A

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-4 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_Strong

The NM_001063.4(TF):c.1330+278G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The gene TF is a known oncogene (CancerMine: 1 oncogene citations). The variant allele was found at a cumulative frequency of 0.311 (AC=47,216) in the gnomAD database across 151,970 control chromosomes, including 7,779 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.408. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (7779 hom., cov: 32)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.490
• Publications: 99 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, ClinGen, Orphanet, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -4 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	B1High frequency in general population		GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.408 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001063.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	TF NM_001063.4	MANE Select	c.1330+278G>A	intron	Intron 11 of 16	Prot: NP_001054.2 UniProt:
	TF NM_001354703.2		c.1198+278G>A	intron	Intron 17 of 22	Prot: NP_001341632.2
	TF NM_001354704.2		c.949+278G>A	intron	Intron 10 of 15	Prot: NP_001341633.2

TF NM_001063.4

MANE Select

HGVSc / HGVSpc.1330+278G>A

Exon rankIntron 11 of 16

intron

Prot: NP_001054.2UniProt: P02787Q06AH7A0PJA6

TF NM_001354703.2

HGVSc / HGVSpc.1198+278G>A

Exon rankIntron 17 of 22

intron

Prot: NP_001341632.2

TF NM_001354704.2

HGVSc / HGVSpc.949+278G>A

Exon rankIntron 10 of 15

intron

Prot: NP_001341633.2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	TF ENST00000402696.9	TSL:1MANE Select	c.1330+278G>A	intron	Intron 11 of 16	Prot: ENSP00000385834.3 UniProt:
	TF ENST00000877249.1		c.682+278G>A	intron	Intron 6 of 11	Prot: ENSP00000547308.1 UniProt:
	TF ENST00000877246.1		c.343+278G>A	intron	Intron 4 of 9	Prot: ENSP00000547305.1 UniProt:

TF ENST00000402696.9

TSL:1MANE Select

HGVSc / HGVSpc.1330+278G>A

Exon rankIntron 11 of 16

intron

Prot: ENSP00000385834.3UniProt: P02787

TF ENST00000877249.1

HGVSc / HGVSpc.682+278G>A

Exon rankIntron 6 of 11

intron

Prot: ENSP00000547308.1UniProt: A0ACI8QAC3

TF ENST00000877246.1

HGVSc / HGVSpc.343+278G>A

Exon rankIntron 4 of 9

intron

Prot: ENSP00000547305.1UniProt: A0ACI8R955

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.311	AC:47170	Hom:7767	AN:151852	Cov:32
GnomAD4 genome	AF: 0.311	AC:47216	Hom:7779	AN:151970	Cov:32
TOPMed (Bravo)	AF: 0.313	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.332	AC:235879	Hom:39943	AN:710756	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.322	AC:755	Hom:125	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.391	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.410	AC:123	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.397	AC:1380	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.399	AC:2889	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.284	AC:50	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.464	AC:56932	Hom:13179	AN:122796	Cov:
Turkish Variome	AF: 0.336	AC:520	Hom:90	AN:1546	Cov:
UK10K	AF: 0.335	AC:2531	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.396	AC:3545	Hom:719	AN:8960	Cov:

Showing 14 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	0.62
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.44
DANN	Benign	0.41
GPN-Star LLR	N/A	0.84
GPN-Star score	N/A	0.84
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	-0.49

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs3811647;

hg19: chr3-133484029;

COSMIC: COSV53918925;

COSMIC: COSV53918925;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar