rs61742136

Variant names:

• chr19-49932858-C-T
• rs61742136
• NM_001193646.2:c.615C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001193646.2(ATF5):​c.615C>T​(p.Thr205Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0299 in 1,612,610 control chromosomes in the GnomAD database, including 980 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 0.036 (137 hom., cov: 28)
  • Exomes 𝑓: 0.029 (843 hom.)
• Consequence: ATF5 NM_001193646.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.16
• Publications: 4 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=2.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF5	NM_001193646.2	c.615C>T	p.Thr205Thr	synonymous_variant	Exon 3 of 3	ENST00000423777.7	NP_001180575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF5	ENST00000423777.7	c.615C>T	p.Thr205Thr	synonymous_variant	Exon 3 of 3	1	NM_001193646.2	ENSP00000396954.1
ENSG00000269179	ENST00000451973.1	n.*77+19033G>A		intron_variant	Intron 2 of 2	2		ENSP00000391489.1

Frequencies

GnomAD3 genomes AF: 0.0361 AC: 5475 AN: 151720 Hom.: 136 Cov.: 28

Gnomad AFR AF: 0.0628

Gnomad AMI AF: 0.00879

Gnomad AMR AF: 0.0232

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.0659

Gnomad FIN AF: 0.0116

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0280

Gnomad OTH AF: 0.0336

GnomAD2 exomes AF: 0.0285 AC: 7051 AN: 247706 AF XY: 0.0300

Gnomad AFR exome AF: 0.0607

Gnomad AMR exome AF: 0.0150

Gnomad ASJ exome AF: 0.0243

Gnomad EAS exome AF: 0.000329

Gnomad FIN exome AF: 0.00907

Gnomad NFE exome AF: 0.0273

Gnomad OTH exome AF: 0.0268

GnomAD4 exome AF: 0.0293 AC: 42818 AN: 1460772 Hom.: 843 Cov.: 39 AF XY: 0.0304 AC XY: 22103 AN XY: 726608

African (AFR) AF: 0.0607 AC: 2029 AN: 33446

American (AMR) AF: 0.0158 AC: 705 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 669 AN: 26106

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39676

South Asian (SAS) AF: 0.0626 AC: 5385 AN: 86082

European-Finnish (FIN) AF: 0.0100 AC: 536 AN: 53338

Middle Eastern (MID) AF: 0.0513 AC: 296 AN: 5768

European-Non Finnish (NFE) AF: 0.0283 AC: 31433 AN: 1111482

Other (OTH) AF: 0.0291 AC: 1758 AN: 60336

GnomAD4 genome AF: 0.0360 AC: 5470 AN: 151838 Hom.: 137 Cov.: 28 AF XY: 0.0355 AC XY: 2637 AN XY: 74184

African (AFR) AF: 0.0625 AC: 2586 AN: 41354

American (AMR) AF: 0.0232 AC: 353 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3472

East Asian (EAS) AF: 0.000968 AC: 5 AN: 5164

South Asian (SAS) AF: 0.0651 AC: 312 AN: 4794

European-Finnish (FIN) AF: 0.0116 AC: 122 AN: 10562

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0280 AC: 1905 AN: 67944

Other (OTH) AF: 0.0351 AC: 74 AN: 2108

Alfa AF: 0.0345 Hom.: 96

Bravo AF: 0.0365

Asia WGS AF: 0.0430 AC: 150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.5
DANN	Benign	0.57
PhyloP100		2.2
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61742136; hg19: chr19-50436115;