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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF4	NM_182810.3 link	c.-219dupC		5_prime_UTR_variant	Exon 1 of 3	ENST00000674920.3	NP_877962.1
ATF4	NM_001675.4 link	c.-821dupC		5_prime_UTR_variant	Exon 1 of 2		NP_001666.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF4	ENST00000674920.3 link	c.-219dupC		5_prime_UTR_variant	Exon 1 of 3		NM_182810.3	ENSP00000501863.1

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 v4.3

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

Publications

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22-39520621-TC-TCC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over