rs8647

chr19-49933723-G-Achr19-49933723-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001193646.2(ATF5):c.*631G>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 0.303 in 153,028 control chromosomes in the GnomAD database, including 7,660 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 (7551 hom., cov: 30)
  • Exomes 𝑓: 0.41 (109 hom.)
• Consequence: ATF5 NM_001193646.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.290

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATF5	NM_001193646.2	c.*631G>A		3_prime_UTR_variant	3/3	ENST00000423777.7
ATF5	NM_001290746.2	c.*631G>A		3_prime_UTR_variant	3/3
ATF5	NM_012068.6	c.*631G>A		3_prime_UTR_variant	4/4
ATF5	XM_011526629.4	c.*631G>A		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATF5	ENST00000423777.7	c.*631G>A		3_prime_UTR_variant	3/3	1	NM_001193646.2	P1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45808 AN: 151710 Hom.: 7552 Cov.: 30

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.315

GnomAD4 exome AF: 0.414 AC: 497 AN: 1200 Hom.: 109 Cov.: 0 AF XY: 0.436 AC XY: 309 AN XY: 708

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.250

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.464

Gnomad4 NFE exome AF: 0.347

Gnomad4 OTH exome AF: 0.432

GnomAD4 genome AF: 0.302 AC: 45835 AN: 151828 Hom.: 7551 Cov.: 30 AF XY: 0.305 AC XY: 22635 AN XY: 74164

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.316

Alfa AF: 0.330 Hom.: 8534

Bravo AF: 0.291

Asia WGS AF: 0.302 AC: 1050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.35
Dann	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs8647; hg19: chr19-50436980; COSMIC: COSV61311973; COSMIC: COSV61311973;