rs1247955

Positions:

• chr12-53570349-G-T

Variant summary

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

The NM_006856.3(ATF7):​c.49-17712C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,990 control chromosomes in the GnomAD database, including 13,317 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 (13317 hom., cov: 31)
• Consequence: ATF7 NM_006856.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.874

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• 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.49-17712C>A		intron_variant		ENST00000420353.7	NP_006847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATF7	ENST00000420353.7	c.49-17712C>A		intron_variant		1	NM_006856.3	ENSP00000399465.1
ATF7-NPFF	ENST00000591834.1	c.49-17712C>A		intron_variant		5		ENSP00000466174.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56744 AN: 151872 Hom.: 13317 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.0431

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.398

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.373 AC: 56748 AN: 151990 Hom.: 13317 Cov.: 31 AF XY: 0.372 AC XY: 27655 AN XY: 74260

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.0434

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.404

Alfa AF: 0.479 Hom.: 8415

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	-0.80
CADD	Benign	4.3
DANN	Benign	0.76

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: rs1247955; hg19: chr12-53964133;