rs1247955

Variant names:

• chr12-53570349-G-T
• rs1247955
• NM_006856.3:c.49-17712C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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]

ENSG00000285692 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.49-17712C>A		intron	N/A	NP_006847.1	P17544-6
	ATF7	NM_001366555.2		c.49-17712C>A		intron	N/A	NP_001353484.1	P17544-1
	ATF7	NM_001366556.2		c.49-17712C>A		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.49-17712C>A		intron	N/A	ENSP00000399465.1	P17544-6
	ATF7-NPFF	ENST00000591834.1	TSL:5	c.49-17712C>A		intron	N/A	ENSP00000466174.1	K7ELQ4
	ATF7	ENST00000548118.6	TSL:1	c.49-17712C>A		intron	N/A	ENSP00000456858.1	P17544-5

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

African (AFR) AF: 0.108 AC: 4488 AN: 41494

American (AMR) AF: 0.387 AC: 5906 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1566 AN: 3468

East Asian (EAS) AF: 0.0434 AC: 225 AN: 5184

South Asian (SAS) AF: 0.397 AC: 1908 AN: 4812

European-Finnish (FIN) AF: 0.529 AC: 5575 AN: 10538

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.524 AC: 35607 AN: 67930

Other (OTH) AF: 0.404 AC: 853 AN: 2110

Alfa AF: 0.478 Hom.: 9415

Bravo AF: 0.348

Asia WGS AF: 0.245 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.3
DANN	Benign	0.76
PhyloP100		0.87
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: rs1247955; hg19: chr12-53964133;