rs12321906

Positions:

• chr12-53522931-T-C

Variant summary

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

The NM_006856.3(ATF7):​c.1234+345A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0445 in 152,324 control chromosomes in the GnomAD database, including 413 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 0.045 (413 hom., cov: 32)
• Consequence: ATF7 NM_006856.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.777

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]

ATF7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATF7	NM_006856.3	c.1234+345A>G		intron_variant		ENST00000420353.7	NP_006847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATF7	ENST00000420353.7	c.1234+345A>G		intron_variant		1	NM_006856.3	ENSP00000399465.1
ATF7-NPFF	ENST00000591834.1	c.1234+345A>G		intron_variant		5		ENSP00000466174.1

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 6760 AN: 152206 Hom.: 411 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0215

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.0300

Gnomad SAS AF: 0.0459

Gnomad FIN AF: 0.00433

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00501

Gnomad OTH AF: 0.0363

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

GnomAD4 genome AF: 0.0445 AC: 6784 AN: 152324 Hom.: 413 Cov.: 32 AF XY: 0.0442 AC XY: 3290 AN XY: 74490

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0214

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.0301

Gnomad4 SAS AF: 0.0464

Gnomad4 FIN AF: 0.00433

Gnomad4 NFE AF: 0.00500

Gnomad4 OTH AF: 0.0359

Alfa AF: 0.0139 Hom.: 105

Bravo AF: 0.0501

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.5
DANN	Benign	0.75

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: rs12321906; hg19: chr12-53916715;