12-53552435-C-G

Variant names:

• chr12-53552435-C-G
• rs1683151
• NM_006856.3:c.145+106G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 -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.

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.145+106G>C		intron	N/A	NP_006847.1	P17544-6
	ATF7	NM_001366555.2		c.145+106G>C		intron	N/A	NP_001353484.1	P17544-1
	ATF7	NM_001366556.2		c.145+106G>C		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.145+106G>C		intron	N/A	ENSP00000399465.1	P17544-6
	ATF7-NPFF	ENST00000591834.1	TSL:5	c.145+106G>C		intron	N/A	ENSP00000466174.1	K7ELQ4
	ATF7	ENST00000548118.6	TSL:1	c.145+106G>C		intron	N/A	ENSP00000456858.1	P17544-5

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

African (AFR) AF: 0.108 AC: 1880 AN: 17476

American (AMR) AF: 0.346 AC: 10050 AN: 29080

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 8521 AN: 18898

East Asian (EAS) AF: 0.0258 AC: 853 AN: 33034

South Asian (SAS) AF: 0.428 AC: 26261 AN: 61362

European-Finnish (FIN) AF: 0.550 AC: 26301 AN: 47788

Middle Eastern (MID) AF: 0.524 AC: 1587 AN: 3028

European-Non Finnish (NFE) AF: 0.525 AC: 229981 AN: 438364

Other (OTH) AF: 0.446 AC: 15222 AN: 34120

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

African (AFR) AF: 0.109 AC: 4502 AN: 41456

American (AMR) AF: 0.389 AC: 5938 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1565 AN: 3468

East Asian (EAS) AF: 0.0436 AC: 226 AN: 5180

South Asian (SAS) AF: 0.397 AC: 1913 AN: 4818

European-Finnish (FIN) AF: 0.532 AC: 5593 AN: 10510

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35625 AN: 67936

Other (OTH) AF: 0.406 AC: 855 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		0.30
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: rs1683151; hg19: chr12-53946219; COSMIC: COSV60644211;