rs1683151

Positions:

• chr12-53552435-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006856.3(ATF7):​c.145+106G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 835,082 control chromosomes in the GnomAD database, including 94,951 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 0.37 (13341 hom., cov: 31)
  • Exomes 𝑓: 0.47 (81610 hom.)
• Consequence: ATF7 NM_006856.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300

Genes affected

ATF7 (HGNC:792): (activating transcription factor 7) Enables several functions, including DNA-binding transcription repressor activity, RNA polymerase II-specific; mitogen-activated protein kinase binding activity; and transcription coactivator binding activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. Biomarker of colorectal cancer. [provided by Alliance of Genome Resources, Apr 2022]

ATF7-NPFF (HGNC:55073): (ATF7-NPFF readthrough) Predicted to enable DNA binding activity and DNA-binding transcription factor activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000285692 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATF7	NM_006856.3	c.145+106G>C		intron_variant		ENST00000420353.7	NP_006847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATF7	ENST00000420353.7	c.145+106G>C		intron_variant		1	NM_006856.3	ENSP00000399465.1
ATF7-NPFF	ENST00000591834.1	c.145+106G>C		intron_variant		5		ENSP00000466174.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56833 AN: 151814 Hom.: 13341 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.0433

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.399

GnomAD4 exome AF: 0.469 AC: 320656 AN: 683150 Hom.: 81610 AF XY: 0.470 AC XY: 168015 AN XY: 357690

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.451

Gnomad4 EAS exome AF: 0.0258

Gnomad4 SAS exome AF: 0.428

Gnomad4 FIN exome AF: 0.550

Gnomad4 NFE exome AF: 0.525

Gnomad4 OTH exome AF: 0.446

GnomAD4 genome AF: 0.374 AC: 56837 AN: 151932 Hom.: 13341 Cov.: 31 AF XY: 0.373 AC XY: 27720 AN XY: 74244

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.0436

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.406

Alfa AF: 0.444 Hom.: 2074

Bravo AF: 0.348

Asia WGS AF: 0.245 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	12
DANN	Benign	0.71

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: rs1683151; hg19: chr12-53946219; COSMIC: COSV60644211;