rs79402775

Variant names:

• chr2-175167648-G-A
• rs79402775
• NM_001880.4:c.-143+402C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-175167648-G-A
• chr2-175167648-G-T

Variant summary

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

The NM_001880.4(ATF2):​c.-143+402C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 500,784 control chromosomes in the GnomAD database, including 870 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 0.030 (179 hom., cov: 32)
  • Exomes 𝑓: 0.043 (691 hom.)
• Consequence: ATF2 NM_001880.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.742
• Publications: 17 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]

MIR933 (HGNC:33676): (microRNA 933) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ENSG00000229750 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001880.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF2	NM_001880.4	MANE Select	c.-143+402C>T		intron	N/A	NP_001871.2
	MIR933	NR_030630.1		n.62C>T		non_coding_transcript_exon	Exon 1 of 1
	ATF2	NM_001256090.2		c.-178+402C>T		intron	N/A	NP_001243019.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF2	ENST00000264110.7	TSL:1 MANE Select	c.-143+402C>T		intron	N/A	ENSP00000264110.2
	ATF2	ENST00000392544.5	TSL:1	c.-178+402C>T		intron	N/A	ENSP00000376327.1
	ATF2	ENST00000426833.7	TSL:1	c.-157+402C>T		intron	N/A	ENSP00000407911.3

Frequencies

GnomAD3 genomes AF: 0.0299 AC: 4552 AN: 152120 Hom.: 179 Cov.: 32

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0996

Gnomad FIN AF: 0.0477

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0209

Gnomad OTH AF: 0.0282

GnomAD2 exomes AF: 0.0443 AC: 8654 AN: 195532 AF XY: 0.0495

Gnomad AFR exome AF: 0.0162

Gnomad AMR exome AF: 0.00885

Gnomad ASJ exome AF: 0.0364

Gnomad EAS exome AF: 0.156

Gnomad FIN exome AF: 0.0482

Gnomad NFE exome AF: 0.0217

Gnomad OTH exome AF: 0.0361

GnomAD4 exome AF: 0.0429 AC: 14952 AN: 348546 Hom.: 691 Cov.: 0 AF XY: 0.0499 AC XY: 9866 AN XY: 197656

African (AFR) AF: 0.0158 AC: 152 AN: 9626

American (AMR) AF: 0.00867 AC: 275 AN: 31704

Ashkenazi Jewish (ASJ) AF: 0.0370 AC: 408 AN: 11028

East Asian (EAS) AF: 0.154 AC: 1696 AN: 11018

South Asian (SAS) AF: 0.109 AC: 6787 AN: 62042

European-Finnish (FIN) AF: 0.0464 AC: 1381 AN: 29734

Middle Eastern (MID) AF: 0.0488 AC: 137 AN: 2806

European-Non Finnish (NFE) AF: 0.0206 AC: 3601 AN: 175180

Other (OTH) AF: 0.0334 AC: 515 AN: 15408

GnomAD4 genome AF: 0.0299 AC: 4548 AN: 152238 Hom.: 179 Cov.: 32 AF XY: 0.0339 AC XY: 2526 AN XY: 74428

African (AFR) AF: 0.0164 AC: 683 AN: 41556

American (AMR) AF: 0.0122 AC: 187 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3470

East Asian (EAS) AF: 0.167 AC: 862 AN: 5170

South Asian (SAS) AF: 0.0997 AC: 480 AN: 4814

European-Finnish (FIN) AF: 0.0477 AC: 506 AN: 10608

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0209 AC: 1422 AN: 68008

Other (OTH) AF: 0.0270 AC: 57 AN: 2114

Alfa AF: 0.0242 Hom.: 141

Bravo AF: 0.0246

Asia WGS AF: 0.0970 AC: 337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.2
DANN	Benign	0.82
PhyloP100		0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs79402775; hg19: chr2-176032376; COSMIC: COSV51373662; COSMIC: COSV51373662;