dbSNP rs4481157: TF:c.-89-2572G>A (chr3-133745840-G-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_001354703.2(TF):c.-89-2572G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 155,178 control chromosomes in the GnomAD database, including 13,240 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 0.41 ( 13089 hom., cov: 32)

Exomes 𝑓: 0.27 ( 151 hom. )

Consequence

TF
NM_001354703.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.596

Publications

11 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 -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 = 0.509 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354703.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	NM_001354703.2		c.-89-2572G>A		intron	N/A	NP_001341632.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000291042	ENST00000460564.5	TSL:4	n.382-7755G>A		intron	N/A
	TF	ENST00000466911.5	TSL:4	c.-499G>A		upstream_gene	N/A	ENSP00000417468.1	C9JB55

Frequencies

GnomAD3 genomes

AF:

0.409

AC:

62158

AN:

151894

Hom.:

13071

Cov.:

show subpopulations

Gnomad AFR

AF:

0.478

Gnomad AMI

AF:

0.265

Gnomad AMR

AF:

0.416

Gnomad ASJ

AF:

0.317

Gnomad EAS

AF:

0.469

Gnomad SAS

AF:

0.527

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.365

Gnomad OTH

AF:

0.370

GnomAD4 exome

AF:

0.268

AC:

847

AN:

3166

Hom.:

151

AF XY:

0.268

AC XY:

424

AN XY:

1582

show subpopulations

African (AFR)

AF:

0.467

AC:

AN:

American (AMR)

AF:

0.293

AC:

153

AN:

522

Ashkenazi Jewish (ASJ)

AF:

0.357

AC:

AN:

East Asian (EAS)

AF:

0.400

AC:

AN:

100

South Asian (SAS)

AF:

0.285

AC:

AN:

144

European-Finnish (FIN)

AF:

0.271

AC:

AN:

Middle Eastern (MID)

AF:

0.167

AC:

AN:

European-Non Finnish (NFE)

AF:

0.252

AC:

543

AN:

2158

Other (OTH)

AF:

0.254

AC:

AN:

122

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.409

AC:

62225

AN:

152012

Hom.:

13089

Cov.:

AF XY:

0.412

AC XY:

30571

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.478

AC:

19832

AN:

41466

American (AMR)

AF:

0.417

AC:

6373

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.317

AC:

1100

AN:

3472

East Asian (EAS)

AF:

0.468

AC:

2410

AN:

5152

South Asian (SAS)

AF:

0.526

AC:

2528

AN:

4806

European-Finnish (FIN)

AF:

0.385

AC:

4069

AN:

10558

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.365

AC:

24818

AN:

67954

Other (OTH)

AF:

0.370

AC:

781

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1906

3811

5717

7622

9528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

606

1212

1818

2424

3030

<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:

0.397

Hom.:

1967

Bravo

AF:

0.414

Asia WGS

AF:

0.511

AC:

1777

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.3

(source)

DANN

Benign

0.54

PhyloP100

0.60

PromoterAI

0.027

Neutral

(source)

Splicing

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