Genetic Variant TF:c.1203+1027G>C (chr3-133760356-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001063.4(TF):c.1203+1027G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.964 in 152,458 control chromosomes in the GnomAD database, including 71,027 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 0.96 ( 70947 hom., cov: 33)

Exomes 𝑓: 0.99 ( 80 hom. )

Consequence

TF
NM_001063.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.42

Publications

6 publications found

Variant links:

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 links:

ACSL3P1 (HGNC:56529): (ACSL3 pseudogene 1)

ACSL3P1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.974 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TF	NM_001063.4	MANE Select	c.1203+1027G>C	intron	N/A	NP_001054.2
TF	NM_001354703.2		c.1071+1027G>C	intron	N/A	NP_001341632.2
TF	NM_001354704.2		c.822+1027G>C	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.1203+1027G>C		intron	N/A	ENSP00000385834.3
	ACSL3P1	ENST00000474389.1	TSL:6	n.57G>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.964

AC:

146743

AN:

152178

Hom.:

70882

Cov.:

show subpopulations

Gnomad AFR

AF:

0.982

Gnomad AMI

AF:

0.997

Gnomad AMR

AF:

0.927

Gnomad ASJ

AF:

0.972

Gnomad EAS

AF:

0.778

Gnomad SAS

AF:

0.928

Gnomad FIN

AF:

0.990

Gnomad MID

AF:

0.962

Gnomad NFE

AF:

0.974

Gnomad OTH

AF:

0.957

GnomAD4 exome

AF:

0.994

AC:

161

AN:

162

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

146

AN:

146

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.964

AC:

146866

AN:

152296

Hom.:

70947

Cov.:

AF XY:

0.962

AC XY:

71649

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.982

AC:

40796

AN:

41550

American (AMR)

AF:

0.927

AC:

14188

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.972

AC:

3376

AN:

3472

East Asian (EAS)

AF:

0.777

AC:

4024

AN:

5176

South Asian (SAS)

AF:

0.929

AC:

4480

AN:

4824

European-Finnish (FIN)

AF:

0.990

AC:

10509

AN:

10620

Middle Eastern (MID)

AF:

0.966

AC:

284

AN:

294

European-Non Finnish (NFE)

AF:

0.974

AC:

66282

AN:

68038

Other (OTH)

AF:

0.955

AC:

2018

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

271

541

812

1082

1353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.970

Hom.:

8904

Bravo

AF:

0.959

Asia WGS

AF:

0.849

AC:

2952

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.27

(source)

DANN

Benign

0.39

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over