Genetic Variant TF:c.502+110G>C (chr3-133754781-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001063.4(TF):c.502+110G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,213,600 control chromosomes in the GnomAD database, including 13 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 0.0016 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 11 hom. )

Consequence

TF
NM_001063.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.213

Publications

5 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 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

TF links:

ENSG00000291042 (HGNC:):

ENSG00000291042 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

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	UniProt
TF	NM_001063.4	MANE Select	c.502+110G>C	intron	N/A	NP_001054.2	P02787
TF	NM_001354703.2		c.370+110G>C	intron	N/A	NP_001341632.2
TF	NM_001354704.2		c.121+110G>C	intron	N/A	NP_001341633.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TF	ENST00000402696.9	TSL:1 MANE Select	c.502+110G>C	intron	N/A	ENSP00000385834.3	P02787
TF	ENST00000877249.1		c.44-2050G>C	intron	N/A	ENSP00000547308.1
TF	ENST00000877246.1		c.216+6197G>C	intron	N/A	ENSP00000547305.1

Frequencies

GnomAD3 genomes

AF:

0.00158

AC:

240

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0204

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.000958

GnomAD4 exome

AF:

0.00116

AC:

1227

AN:

1061284

Hom.:

AF XY:

0.00109

AC XY:

593

AN XY:

545412

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25580

American (AMR)

AF:

0.0000228

AC:

AN:

43788

Ashkenazi Jewish (ASJ)

AF:

0.0000423

AC:

AN:

23660

East Asian (EAS)

AF:

0.0000265

AC:

AN:

37794

South Asian (SAS)

AF:

0.0000903

AC:

AN:

77500

European-Finnish (FIN)

AF:

0.0204

AC:

1063

AN:

52096

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3524

European-Non Finnish (NFE)

AF:

0.000139

AC:

104

AN:

750164

Other (OTH)

AF:

0.00106

AC:

AN:

47178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

130

196

261

326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00158

AC:

240

AN:

152316

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

165

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41576

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0204

AC:

217

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68024

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000222

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.7

(source)

DANN

Benign

0.66

PhyloP100

0.21

Mutation Taster

=100/0

polymorphism

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over