12-50809588-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005171.5(ATF1):c.327C>T(p.Tyr109Tyr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,608,190 control chromosomes in the GnomAD database, including 124,850 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13308 hom., cov: 31)

Exomes 𝑓: 0.39 ( 111542 hom. )

Consequence

ATF1
NM_005171.5 splice_region, synonymous

Scores

Splicing: ADA: 0.004790

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.01

Publications

32 publications found

Variant links:

Genes affected

ATF1 (HGNC:783): (activating transcription factor 1) This gene encodes an activating transcription factor, which belongs to the ATF subfamily and bZIP (basic-region leucine zipper) family. It influences cellular physiologic processes by regulating the expression of downstream target genes, which are related to growth, survival, and other cellular activities. This protein is phosphorylated at serine 63 in its kinase-inducible domain by serine/threonine kinases, cAMP-dependent protein kinase A, calmodulin-dependent protein kinase I/II, mitogen- and stress-activated protein kinase and cyclin-dependent kinase 3 (cdk-3). Its phosphorylation enhances its transactivation and transcriptional activities, and enhances cell transformation. Fusion of this gene and FUS on chromosome 16 or EWSR1 on chromosome 22 induced by translocation generates chimeric proteins in angiomatoid fibrous histiocytoma and clear cell sarcoma. This gene has a pseudogene on chromosome 6. [provided by RefSeq, Aug 2010]

ATF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 12-50809588-C-T is Benign according to our data. Variant chr12-50809588-C-T is described in ClinVar as Benign. ClinVar VariationId is 1285794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF1	NM_005171.5 link	c.327C>T	p.Tyr109Tyr	splice_region_variant, synonymous_variant	Exon 4 of 7	ENST00000262053.8	NP_005162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF1	ENST00000262053.8 link	c.327C>T	p.Tyr109Tyr	splice_region_variant, synonymous_variant	Exon 4 of 7	1	NM_005171.5	ENSP00000262053.3

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

61769

AN:

151332

Hom.:

13289

Cov.:

show subpopulations

Gnomad AFR

AF:

0.538

Gnomad AMI

AF:

0.273

Gnomad AMR

AF:

0.294

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.274

Gnomad SAS

AF:

0.359

Gnomad FIN

AF:

0.322

Gnomad MID

AF:

0.357

Gnomad NFE

AF:

0.390

Gnomad OTH

AF:

0.410

GnomAD2 exomes

AF:

0.353

AC:

88402

AN:

250102

AF XY:

0.356

show subpopulations

Gnomad AFR exome

AF:

0.543

Gnomad AMR exome

AF:

0.226

Gnomad ASJ exome

AF:

0.289

Gnomad EAS exome

AF:

0.265

Gnomad FIN exome

AF:

0.327

Gnomad NFE exome

AF:

0.387

Gnomad OTH exome

AF:

0.360

GnomAD4 exome

AF:

0.387

AC:

563475

AN:

1456742

Hom.:

111542

Cov.:

AF XY:

0.386

AC XY:

279889

AN XY:

724926

show subpopulations

African (AFR)

AF:

0.535

AC:

17865

AN:

33380

American (AMR)

AF:

0.235

AC:

10413

AN:

44244

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

7571

AN:

26076

East Asian (EAS)

AF:

0.317

AC:

12585

AN:

39672

South Asian (SAS)

AF:

0.357

AC:

30669

AN:

85916

European-Finnish (FIN)

AF:

0.338

AC:

18023

AN:

53322

Middle Eastern (MID)

AF:

0.373

AC:

2133

AN:

5714

European-Non Finnish (NFE)

AF:

0.398

AC:

441202

AN:

1108210

Other (OTH)

AF:

0.382

AC:

23014

AN:

60208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

15896

31792

47687

63583

79479

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13780

27560

41340

55120

68900

<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:

0.408

AC:

61818

AN:

151448

Hom.:

13308

Cov.:

AF XY:

0.400

AC XY:

29613

AN XY:

73968

show subpopulations

African (AFR)

AF:

0.538

AC:

22203

AN:

41296

American (AMR)

AF:

0.293

AC:

4467

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

1021

AN:

3464

East Asian (EAS)

AF:

0.273

AC:

1400

AN:

5130

South Asian (SAS)

AF:

0.359

AC:

1726

AN:

4806

European-Finnish (FIN)

AF:

0.322

AC:

3374

AN:

10464

Middle Eastern (MID)

AF:

0.369

AC:

107

AN:

290

European-Non Finnish (NFE)

AF:

0.390

AC:

26415

AN:

67770

Other (OTH)

AF:

0.408

AC:

859

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1733

3467

5200

6934

8667

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

586

1172

1758

2344

2930

<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:

0.389

Hom.:

42499

Bravo

AF:

0.413

Asia WGS

AF:

0.351

AC:

1221

AN:

3478

EpiCase

AF:

0.386

EpiControl

AF:

0.394

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 29547645, 26553438) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

3.0

Mutation Taster

=44/56

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0048

dbscSNV1_RF

Benign

0.084

SpliceAI score (max)

0.030

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over