22-39520621-TC-TCC

Position:

• chr22-39520621-TC-TCC

Variant summary

Our verdict is Benign. Variant got -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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ATF4	NM_182810.3	c.-219dupC		5_prime_UTR_variant	1/3	ENST00000674920.3	NP_877962.1
ATF4	NM_001675.4	c.-821dupC		5_prime_UTR_variant	1/2		NP_001666.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATF4	ENST00000674920	c.-219dupC		5_prime_UTR_variant	1/3		NM_182810.3	ENSP00000501863.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45864 AN: 152054 Hom.: 7024 Cov.: 0

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.: 45 Cov.: 0 AF XY: 0.349 AC XY: 164 AN XY: 470

Gnomad4 EAS exome AF: 0.280

Gnomad4 SAS exome AF: 0.241

Gnomad4 FIN exome AF: 0.386

Gnomad4 NFE exome AF: 0.261

Gnomad4 OTH exome AF: 0.286

GnomAD4 genome AF: 0.302 AC: 45885 AN: 152170 Hom.: 7024 Cov.: 0 AF XY: 0.301 AC XY: 22378 AN XY: 74384

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.310

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

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

LitVar

Other links and lift over

dbSNP: rs17001266; hg19: chr22-39916626;