rs283525

Variant names:

• chr19-49932490-T-C
• rs283525
• NM_001193646.2:c.247T>C

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.247T>C​(p.Leu83Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 1,591,096 control chromosomes in the GnomAD database, including 288,886 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 0.63 (27666 hom., cov: 18)
  • Exomes 𝑓: 0.60 (261220 hom.)
• Consequence: ATF5 NM_001193646.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830
• Publications: 19 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:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=0.083 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF5	NM_001193646.2	c.247T>C	p.Leu83Leu	synonymous_variant	Exon 3 of 3	ENST00000423777.7	NP_001180575.1
ATF5	NM_001290746.2	c.247T>C	p.Leu83Leu	synonymous_variant	Exon 3 of 3		NP_001277675.1
ATF5	NM_012068.6	c.247T>C	p.Leu83Leu	synonymous_variant	Exon 4 of 4		NP_036200.2
ATF5	XM_011526629.4	c.247T>C	p.Leu83Leu	synonymous_variant	Exon 3 of 3		XP_011524931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF5	ENST00000423777.7	c.247T>C	p.Leu83Leu	synonymous_variant	Exon 3 of 3	1	NM_001193646.2	ENSP00000396954.1
ENSG00000269179	ENST00000451973.1	n.*77+19401A>G		intron_variant	Intron 2 of 2	2		ENSP00000391489.1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 86725 AN: 138208 Hom.: 27626 Cov.: 18

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.613

GnomAD2 exomes AF: 0.621 AC: 154285 AN: 248504 AF XY: 0.616

Gnomad AFR exome AF: 0.725

Gnomad AMR exome AF: 0.651

Gnomad ASJ exome AF: 0.535

Gnomad EAS exome AF: 0.705

Gnomad FIN exome AF: 0.667

Gnomad NFE exome AF: 0.588

Gnomad OTH exome AF: 0.594

GnomAD4 exome AF: 0.597 AC: 867199 AN: 1452776 Hom.: 261220 Cov.: 35 AF XY: 0.597 AC XY: 431442 AN XY: 723104

African (AFR) AF: 0.727 AC: 24169 AN: 33250

American (AMR) AF: 0.650 AC: 29009 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 14013 AN: 26042

East Asian (EAS) AF: 0.754 AC: 29876 AN: 39614

South Asian (SAS) AF: 0.598 AC: 51481 AN: 86040

European-Finnish (FIN) AF: 0.667 AC: 35506 AN: 53196

Middle Eastern (MID) AF: 0.552 AC: 3139 AN: 5682

European-Non Finnish (NFE) AF: 0.584 AC: 644417 AN: 1104272

Other (OTH) AF: 0.593 AC: 35589 AN: 60052

GnomAD4 genome AF: 0.628 AC: 86833 AN: 138320 Hom.: 27666 Cov.: 18 AF XY: 0.627 AC XY: 41742 AN XY: 66536

African (AFR) AF: 0.716 AC: 25654 AN: 35846

American (AMR) AF: 0.594 AC: 8003 AN: 13472

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1744 AN: 3356

East Asian (EAS) AF: 0.698 AC: 3202 AN: 4590

South Asian (SAS) AF: 0.599 AC: 2514 AN: 4200

European-Finnish (FIN) AF: 0.650 AC: 5656 AN: 8698

Middle Eastern (MID) AF: 0.552 AC: 160 AN: 290

European-Non Finnish (NFE) AF: 0.588 AC: 38301 AN: 65166

Other (OTH) AF: 0.613 AC: 1120 AN: 1828

Alfa AF: 0.607 Hom.: 54802

Bravo AF: 0.641

EpiCase AF: 0.594

EpiControl AF: 0.585

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.40
PhyloP100		0.083
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs283525; hg19: chr19-50435747; COSMIC: COSV61313087; COSMIC: COSV61313087;