Genetic Variant ATF4:c.-219dupC (chr22-39520621-T-TC) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_182810.3(ATF4):c.-219dupC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7024 hom., cov: 0)

Exomes 𝑓: 0.34 ( 45 hom. )

Consequence

ATF4
NM_182810.3 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.227

Publications

3 publications found

Variant links:

Genes affected

ATF4 (HGNC:786): (activating transcription factor 4) This gene encodes a transcription factor that was originally identified as a widely expressed mammalian DNA binding protein that could bind a tax-responsive enhancer element in the LTR of HTLV-1. The encoded protein was also isolated and characterized as the cAMP-response element binding protein 2 (CREB-2). The protein encoded by this gene belongs to a family of DNA-binding proteins that includes the AP-1 family of transcription factors, cAMP-response element binding proteins (CREBs) and CREB-like proteins. These transcription factors share a leucine zipper region that is involved in protein-protein interactions, located C-terminal to a stretch of basic amino acids that functions as a DNA binding domain. Two alternative transcripts encoding the same protein have been described. Two pseudogenes are located on the X chromosome at q28 in a region containing a large inverted duplication. [provided by RefSeq, Sep 2011]

ATF4 links:

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ACMG classification

Classification was made for transcript

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

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182810.3. 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
	ATF4	NM_182810.3	MANE Select	c.-219dupC		5_prime_UTR	Exon 1 of 3	NP_877962.1	P18848
	ATF4	NM_001675.4		c.-821dupC		5_prime_UTR	Exon 1 of 2	NP_001666.2	P18848

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATF4	ENST00000674920.3	MANE Select	c.-219dupC	5_prime_UTR	Exon 1 of 3	ENSP00000501863.1	P18848
ATF4	ENST00000337304.2	TSL:1	c.-821dupC	5_prime_UTR	Exon 1 of 2	ENSP00000336790.2	P18848
ATF4	ENST00000396680.3	TSL:1	c.-315dupC	5_prime_UTR	Exon 1 of 3	ENSP00000379912.1	P18848

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45864

AN:

152054

Hom.:

7024

Cov.:

show subpopulations

Gnomad AFR

AF:

0.281

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.339

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.310

GnomAD4 exome

AF:

0.337

AC:

243

AN:

722

Hom.:

Cov.:

AF XY:

0.349

AC XY:

164

AN XY:

470

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.280

AC:

AN:

South Asian (SAS)

AF:

0.241

AC:

AN:

European-Finnish (FIN)

AF:

0.386

AC:

165

AN:

428

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.261

AC:

AN:

142

Other (OTH)

AF:

0.286

AC:

AN:

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

Exome Het

Exome Hom

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:

0.302

AC:

45885

AN:

152170

Hom.:

7024

Cov.:

AF XY:

0.301

AC XY:

22378

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.281

AC:

11669

AN:

41516

American (AMR)

AF:

0.286

AC:

4368

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.351

AC:

1217

AN:

3468

East Asian (EAS)

AF:

0.197

AC:

1018

AN:

5174

South Asian (SAS)

AF:

0.339

AC:

1638

AN:

4826

European-Finnish (FIN)

AF:

0.331

AC:

3510

AN:

10592

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.315

AC:

21395

AN:

67980

Other (OTH)

AF:

0.310

AC:

654

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1713

3427

5140

6854

8567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<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:

0.199

Hom.:

431

Bravo

AF:

0.295

Asia WGS

AF:

0.330

AC:

1149

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.23

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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22-39520621-TC-TCC

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