rs61742136

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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

GnomAD3 exomes AF: 0.0285 AC: 7051 AN: 247706 Hom.: 174 AF XY: 0.0300 AC XY: 4020 AN XY: 134142

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 SAS exome AF: 0.0632

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

Gnomad4 AFR exome AF: 0.0607

Gnomad4 AMR exome AF: 0.0158

Gnomad4 ASJ exome AF: 0.0256

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.0626

Gnomad4 FIN exome AF: 0.0100

Gnomad4 NFE exome AF: 0.0283

Gnomad4 OTH exome AF: 0.0291

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

Gnomad4 AFR AF: 0.0625

Gnomad4 AMR AF: 0.0232

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.000968

Gnomad4 SAS AF: 0.0651

Gnomad4 FIN AF: 0.0116

Gnomad4 NFE AF: 0.0280

Gnomad4 OTH AF: 0.0351

Alfa AF: 0.0321 Hom.: 55

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
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs61742136; hg19: chr19-50436115;