rs3755488

Variant names:

• chr2-175079323-C-G
• rs3755488
• NM_001880.4:c.1291+1337G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001880.4(ATF2):​c.1291+1337G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0679 in 152,070 control chromosomes in the GnomAD database, including 356 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 0.068 (356 hom., cov: 32)
• Consequence: ATF2 NM_001880.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166
• Publications: 0 publications found

Genes affected

ATF2 (HGNC:784): (activating transcription factor 2) This gene encodes a transcription factor that is a member of the leucine zipper family of DNA binding proteins. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions This protein binds to the cAMP-responsive element (CRE), an octameric palindrome. It forms a homodimer or a heterodimer with c-Jun and stimulates CRE-dependent transcription. This protein is also a histone acetyltransferase (HAT) that specifically acetylates histones H2B and H4 in vitro; thus it may represent a class of sequence-specific factors that activate transcription by direct effects on chromatin components. The encoded protein may also be involved in cell's DNA damage response independent of its role in transcriptional regulation. Several alternatively spliced transcript variants have been found for this gene [provided by RefSeq, Jan 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF2	NM_001880.4	c.1291+1337G>C		intron_variant	Intron 13 of 13	ENST00000264110.7	NP_001871.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF2	ENST00000264110.7	c.1291+1337G>C		intron_variant	Intron 13 of 13	1	NM_001880.4	ENSP00000264110.2

Frequencies

GnomAD3 genomes AF: 0.0679 AC: 10318 AN: 151954 Hom.: 357 Cov.: 32

Gnomad AFR AF: 0.0718

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0664

Gnomad ASJ AF: 0.0787

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0746

Gnomad FIN AF: 0.0423

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0654

Gnomad OTH AF: 0.0709

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0679 AC: 10325 AN: 152070 Hom.: 356 Cov.: 32 AF XY: 0.0677 AC XY: 5030 AN XY: 74328

African (AFR) AF: 0.0718 AC: 2978 AN: 41484

American (AMR) AF: 0.0664 AC: 1013 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0787 AC: 273 AN: 3470

East Asian (EAS) AF: 0.122 AC: 632 AN: 5186

South Asian (SAS) AF: 0.0742 AC: 358 AN: 4824

European-Finnish (FIN) AF: 0.0423 AC: 448 AN: 10586

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.0654 AC: 4445 AN: 67954

Other (OTH) AF: 0.0701 AC: 148 AN: 2110

Alfa AF: 0.0644 Hom.: 43

Bravo AF: 0.0694

Asia WGS AF: 0.107 AC: 370 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.6
DANN	Benign	0.49
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3755488; hg19: chr2-175944051;