rs11169571

Positions:

• chr12-50819982-T-C

Variant summary

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

The NM_005171.5(ATF1):​c.*203T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 400,498 control chromosomes in the GnomAD database, including 27,748 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 0.36 (10286 hom., cov: 32)
  • Exomes 𝑓: 0.37 (17462 hom.)
• Consequence: ATF1 NM_005171.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161

Genes affected

ATF1 (HGNC:783): (activating transcription factor 1) This gene encodes an activating transcription factor, which belongs to the ATF subfamily and bZIP (basic-region leucine zipper) family. It influences cellular physiologic processes by regulating the expression of downstream target genes, which are related to growth, survival, and other cellular activities. This protein is phosphorylated at serine 63 in its kinase-inducible domain by serine/threonine kinases, cAMP-dependent protein kinase A, calmodulin-dependent protein kinase I/II, mitogen- and stress-activated protein kinase and cyclin-dependent kinase 3 (cdk-3). Its phosphorylation enhances its transactivation and transcriptional activities, and enhances cell transformation. Fusion of this gene and FUS on chromosome 16 or EWSR1 on chromosome 22 induced by translocation generates chimeric proteins in angiomatoid fibrous histiocytoma and clear cell sarcoma. This gene has a pseudogene on chromosome 6. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATF1	NM_005171.5	c.*203T>C		3_prime_UTR_variant	7/7	ENST00000262053.8	NP_005162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATF1	ENST00000262053.8	c.*203T>C		3_prime_UTR_variant	7/7	1	NM_005171.5	ENSP00000262053	P1
ATF1	ENST00000551831.5	c.*616T>C		3_prime_UTR_variant, NMD_transcript_variant	6/6	2		ENSP00000448987

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55161 AN: 151846 Hom.: 10285 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.384

GnomAD4 exome AF: 0.370 AC: 92000 AN: 248534 Hom.: 17462 Cov.: 4 AF XY: 0.371 AC XY: 47393 AN XY: 127816

Gnomad4 AFR exome AF: 0.373

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.349

Gnomad4 SAS exome AF: 0.344

Gnomad4 FIN exome AF: 0.347

Gnomad4 NFE exome AF: 0.388

Gnomad4 OTH exome AF: 0.363

GnomAD4 genome AF: 0.363 AC: 55183 AN: 151964 Hom.: 10286 Cov.: 32 AF XY: 0.358 AC XY: 26565 AN XY: 74258

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.382

Alfa AF: 0.377 Hom.: 21334

Bravo AF: 0.363

Asia WGS AF: 0.342 AC: 1189 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.8
DANN	Benign	0.58

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: rs11169571; hg19: chr12-51213765; COSMIC: COSV50395912;