rs12321906

Variant names:

• chr12-53522931-T-C
• rs12321906
• NM_006856.3:c.1234+345A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006856.3. 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
	ATF7	NM_006856.3	MANE Select	c.1234+345A>G		intron	N/A	NP_006847.1	P17544-6
	ATF7	NM_001366555.2		c.1267+345A>G		intron	N/A	NP_001353484.1	P17544-1
	ATF7	NM_001366556.2		c.1234+345A>G		intron	N/A	NP_001353485.1	P17544-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF7	ENST00000420353.7	TSL:1 MANE Select	c.1234+345A>G		intron	N/A	ENSP00000399465.1	P17544-6
	ATF7-NPFF	ENST00000591834.1	TSL:5	c.1234+345A>G		intron	N/A	ENSP00000466174.1	K7ELQ4
	ATF7	ENST00000546661.1	TSL:1	n.419+345A>G		intron	N/A

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

African (AFR) AF: 0.134 AC: 5588 AN: 41556

American (AMR) AF: 0.0214 AC: 328 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.0301 AC: 156 AN: 5190

South Asian (SAS) AF: 0.0464 AC: 224 AN: 4830

European-Finnish (FIN) AF: 0.00433 AC: 46 AN: 10614

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00500 AC: 340 AN: 68034

Other (OTH) AF: 0.0359 AC: 76 AN: 2116

Alfa AF: 0.0224 Hom.: 343

Bravo AF: 0.0501

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.5
DANN	Benign	0.75
PhyloP100		0.78
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: rs12321906; hg19: chr12-53916715;