dbSNP rs8177326: TF:c.1204-1810C>A (chr3-133762372-C-A) – 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.1204-1810C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0328 in 153,506 control chromosomes in the GnomAD database, including 223 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 0.033 ( 222 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1 hom. )

Consequence

TF
NM_001063.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.544

Publications

1 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:

Genome browser will be placed here

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=-0.84).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.104 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	UniProt
TF	NM_001063.4	MANE Select	c.1204-1810C>A	intron	N/A	NP_001054.2	P02787
TF	NM_001354703.2		c.1072-1810C>A	intron	N/A	NP_001341632.2
TF	NM_001354704.2		c.823-1810C>A	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.1204-1810C>A	intron	N/A	ENSP00000385834.3	P02787
TF	ENST00000877249.1		c.556-1810C>A	intron	N/A	ENSP00000547308.1
TF	ENST00000877246.1		c.217-1810C>A	intron	N/A	ENSP00000547305.1

Frequencies

GnomAD3 genomes

AF:

0.0326

AC:

4960

AN:

152092

Hom.:

214

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00674

Gnomad AMI

AF:

0.0473

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.0499

Gnomad EAS

AF:

0.00385

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.0323

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0342

Gnomad OTH

AF:

0.0388

GnomAD4 exome

AF:

0.0386

AC:

AN:

1296

Hom.:

Cov.:

AF XY:

0.0332

AC XY:

AN XY:

784

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.167

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

AN:

188

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00424

AC:

AN:

236

European-Finnish (FIN)

AF:

0.0495

AC:

AN:

202

Middle Eastern (MID)

AF:

0.0110

AC:

AN:

364

European-Non Finnish (NFE)

AF:

0.0349

AC:

AN:

172

Other (OTH)

AF:

0.0814

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

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:

0.0327

AC:

4978

AN:

152210

Hom.:

222

Cov.:

AF XY:

0.0325

AC XY:

2420

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.00672

AC:

279

AN:

41540

American (AMR)

AF:

0.108

AC:

1651

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0499

AC:

173

AN:

3470

East Asian (EAS)

AF:

0.00386

AC:

AN:

5186

South Asian (SAS)

AF:

0.0145

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0323

AC:

342

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0341

AC:

2321

AN:

67988

Other (OTH)

AF:

0.0374

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

229

457

686

914

1143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0317

Hom.:

Bravo

AF:

0.0399

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.5

(source)

DANN

Benign

0.44

PhyloP100

0.54

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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