dbSNP rs8177260: TF:c.1203+2285T>A (chr3-133761614-T-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.1203+2285T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,252 control chromosomes in the GnomAD database, including 8,618 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 0.33 ( 8608 hom., cov: 33)

Exomes 𝑓: 0.49 ( 10 hom. )

Consequence

TF
NM_001063.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.23

Publications

3 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=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4 link	c.1203+2285T>A	intron_variant	Intron 9 of 16	ENST00000402696.9	NP_001054.2	P02787Q06AH7A0PJA6
ACSL3P1		n.133761614T>A	intragenic_variant
TF	NM_001354703.2 link	c.1071+2285T>A	intron_variant	Intron 15 of 22		NP_001341632.2
TF	NM_001354704.2 link	c.822+2285T>A	intron_variant	Intron 8 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9 link	c.1203+2285T>A		intron_variant	Intron 9 of 16	1	NM_001063.4	ENSP00000385834.3		P02787
ACSL3P1	ENST00000474389.1 link	n.1168T>A		non_coding_transcript_exon_variant	Exon 2 of 2	6

Frequencies

GnomAD3 genomes

AF:

0.330

AC:

50235

AN:

152042

Hom.:

8588

Cov.:

show subpopulations

Gnomad AFR

AF:

0.268

Gnomad AMI

AF:

0.310

Gnomad AMR

AF:

0.401

Gnomad ASJ

AF:

0.290

Gnomad EAS

AF:

0.428

Gnomad SAS

AF:

0.429

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.333

GnomAD4 exome

AF:

0.489

AC:

AN:

Hom.:

Cov.:

AF XY:

0.462

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.515

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.409

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.641

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.331

AC:

50298

AN:

152160

Hom.:

8608

Cov.:

AF XY:

0.331

AC XY:

24623

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.268

AC:

11120

AN:

41506

American (AMR)

AF:

0.402

AC:

6153

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

1004

AN:

3466

East Asian (EAS)

AF:

0.427

AC:

2212

AN:

5182

South Asian (SAS)

AF:

0.428

AC:

2063

AN:

4820

European-Finnish (FIN)

AF:

0.292

AC:

3090

AN:

10576

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.347

AC:

23582

AN:

67994

Other (OTH)

AF:

0.339

AC:

716

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1737

3474

5211

6948

8685

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

522

1044

1566

2088

2610

<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:

0.339

Hom.:

1220

Bravo

AF:

0.336

Asia WGS

AF:

0.426

AC:

1479

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.0

(source)

DANN

Benign

0.84

PhyloP100

2.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over