rs8667

Variant names:

• chr19-49933114-G-A
• rs8667
• NM_001193646.2:c.*22G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-49933114-G-A
• chr19-49933114-G-C

Variant summary

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

The NM_001193646.2(ATF5):​c.*22G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,547,772 control chromosomes in the GnomAD database, including 87,077 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 0.30 (7618 hom., cov: 30)
  • Exomes 𝑓: 0.33 (79459 hom.)
• Consequence: ATF5 NM_001193646.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.392
• Publications: 24 publications found

Genes affected

ATF5 (HGNC:790): (activating transcription factor 5) Enables several functions, including DNA-binding transcription activator activity, RNA polymerase II-specific; RNA polymerase II transcription regulatory region sequence-specific DNA binding activity; and tubulin binding activity. Involved in several processes, including fat cell differentiation; regulation of cell cycle process; and regulation of transcription, DNA-templated. Located in centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000269179 (HGNC:):

MIR4751 (HGNC:41819): (microRNA 4751) 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193646.2. 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
	ATF5	NM_001193646.2	MANE Select	c.*22G>A		3_prime_UTR	Exon 3 of 3	NP_001180575.1	Q9Y2D1
	ATF5	NM_001290746.2		c.*22G>A		3_prime_UTR	Exon 3 of 3	NP_001277675.1	Q9Y2D1
	ATF5	NM_012068.6		c.*22G>A		3_prime_UTR	Exon 4 of 4	NP_036200.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF5	ENST00000423777.7	TSL:1 MANE Select	c.*22G>A		3_prime_UTR	Exon 3 of 3	ENSP00000396954.1	Q9Y2D1
	ENSG00000269179	ENST00000451973.1	TSL:2	n.*77+18777C>T		intron	N/A	ENSP00000391489.1	H7BZU6
	ATF5	ENST00000595125.5	TSL:2	c.*22G>A		3_prime_UTR	Exon 4 of 4	ENSP00000470633.1	Q9Y2D1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46063 AN: 151776 Hom.: 7619 Cov.: 30

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.317

GnomAD2 exomes AF: 0.340 AC: 66916 AN: 196838 AF XY: 0.335

Gnomad AFR exome AF: 0.178

Gnomad AMR exome AF: 0.373

Gnomad ASJ exome AF: 0.287

Gnomad EAS exome AF: 0.447

Gnomad FIN exome AF: 0.462

Gnomad NFE exome AF: 0.345

Gnomad OTH exome AF: 0.331

GnomAD4 exome AF: 0.332 AC: 464104 AN: 1395878 Hom.: 79459 Cov.: 37 AF XY: 0.329 AC XY: 225463 AN XY: 685780

African (AFR) AF: 0.173 AC: 5509 AN: 31772

American (AMR) AF: 0.366 AC: 13833 AN: 37792

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 6348 AN: 22112

East Asian (EAS) AF: 0.432 AC: 16764 AN: 38838

South Asian (SAS) AF: 0.200 AC: 15315 AN: 76580

European-Finnish (FIN) AF: 0.462 AC: 23303 AN: 50438

Middle Eastern (MID) AF: 0.205 AC: 1111 AN: 5410

European-Non Finnish (NFE) AF: 0.338 AC: 364014 AN: 1075520

Other (OTH) AF: 0.312 AC: 17907 AN: 57416

GnomAD4 genome AF: 0.303 AC: 46091 AN: 151894 Hom.: 7618 Cov.: 30 AF XY: 0.307 AC XY: 22754 AN XY: 74222

African (AFR) AF: 0.175 AC: 7232 AN: 41432

American (AMR) AF: 0.342 AC: 5218 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 945 AN: 3470

East Asian (EAS) AF: 0.443 AC: 2278 AN: 5144

South Asian (SAS) AF: 0.205 AC: 987 AN: 4808

European-Finnish (FIN) AF: 0.458 AC: 4837 AN: 10562

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.349 AC: 23699 AN: 67896

Other (OTH) AF: 0.318 AC: 671 AN: 2112

Alfa AF: 0.330 Hom.: 5680

Bravo AF: 0.293

Asia WGS AF: 0.304 AC: 1058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.76
PhyloP100		0.39
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: rs8667; hg19: chr19-50436371; COSMIC: COSV61311845; COSMIC: COSV61311845;