rs11169571

Variant names:

• chr12-50819982-T-C
• rs11169571
• NM_005171.5:c.*203T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 40 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005171.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF1	NM_005171.5	MANE Select	c.*203T>C		3_prime_UTR	Exon 7 of 7	NP_005162.1	P18846-1
	ATF1	NM_001412960.1		c.*203T>C		3_prime_UTR	Exon 7 of 7	NP_001399889.1
	ATF1	NM_001412961.1		c.*203T>C		3_prime_UTR	Exon 7 of 7	NP_001399890.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF1	ENST00000262053.8	TSL:1 MANE Select	c.*203T>C		3_prime_UTR	Exon 7 of 7	ENSP00000262053.3	P18846-1
	ATF1	ENST00000862770.1		c.*203T>C		3_prime_UTR	Exon 8 of 8	ENSP00000532829.1
	ATF1	ENST00000862771.1		c.*203T>C		3_prime_UTR	Exon 8 of 8	ENSP00000532830.1

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

African (AFR) AF: 0.373 AC: 2483 AN: 6648

American (AMR) AF: 0.261 AC: 2160 AN: 8280

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 2460 AN: 8568

East Asian (EAS) AF: 0.349 AC: 6886 AN: 19736

South Asian (SAS) AF: 0.344 AC: 3665 AN: 10662

European-Finnish (FIN) AF: 0.347 AC: 6323 AN: 18238

Middle Eastern (MID) AF: 0.351 AC: 419 AN: 1194

European-Non Finnish (NFE) AF: 0.388 AC: 61870 AN: 159402

Other (OTH) AF: 0.363 AC: 5734 AN: 15806

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

African (AFR) AF: 0.378 AC: 15670 AN: 41462

American (AMR) AF: 0.277 AC: 4235 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1018 AN: 3468

East Asian (EAS) AF: 0.275 AC: 1423 AN: 5178

South Asian (SAS) AF: 0.360 AC: 1736 AN: 4816

European-Finnish (FIN) AF: 0.324 AC: 3415 AN: 10532

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26523 AN: 67924

Other (OTH) AF: 0.382 AC: 806 AN: 2110

Alfa AF: 0.376 Hom.: 42335

Bravo AF: 0.363

Asia WGS AF: 0.342 AC: 1189 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.8
DANN	Benign	0.58
PhyloP100		-0.16
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: rs11169571; hg19: chr12-51213765; COSMIC: COSV50395912;