12-53626419-T-G

Position:

• chr12-53626419-T-G

Variant summary

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

The 12-53626419-T-G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,466 control chromosomes in the GnomAD database, including 10,111 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 0.36 (10084 hom., cov: 32)
  • Exomes 𝑓: 0.30 (27 hom.)
• Consequence: ATF7 NM_006856.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATF7	NM_006856.3			upstream_gene_variant		ENST00000420353.7	NP_006847.1
ATF7-NPFF	NR_159377.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATF7	ENST00000420353.7			upstream_gene_variant		1	NM_006856.3	ENSP00000399465	P1
ATF7	ENST00000591397.1			upstream_gene_variant		1		ENSP00000465192
ATF7	ENST00000548446.6			upstream_gene_variant		2		ENSP00000449938
ATF7	ENST00000589726.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54233 AN: 151718 Hom.: 10075 Cov.: 32

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.369

GnomAD4 exome AF: 0.305 AC: 192 AN: 630 Hom.: 27 Cov.: 0 AF XY: 0.320 AC XY: 132 AN XY: 412

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.318

Gnomad4 NFE exome AF: 0.285

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.358 AC: 54283 AN: 151836 Hom.: 10084 Cov.: 32 AF XY: 0.364 AC XY: 27010 AN XY: 74176

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.366

Alfa AF: 0.318 Hom.: 7355

Bravo AF: 0.364

Asia WGS AF: 0.534 AC: 1854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.6
DANN	Benign	0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10876469; hg19: chr12-54020203; COSMIC: COSV69392993;