12-133201580-G-A

Variant names:

• chr12-133201580-G-A
• rs7960480
• NM_003415.3:c.458-564G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003415.3(ZNF268):​c.458-564G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,788 control chromosomes in the GnomAD database, including 9,400 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 0.34 (9400 hom., cov: 32)
• Consequence: ZNF268 NM_003415.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299
• Publications: 8 publications found

Genes affected

ZNF268 (HGNC:13061): (zinc finger protein 268) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in several processes, including positive regulation of NIK/NF-kappaB signaling; positive regulation of nitrogen compound metabolic process; and regulation of apoptotic process. Located in actin cytoskeleton; cytosol; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000256825 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003415.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF268	NM_003415.3	MANE Select	c.458-564G>A		intron	N/A	NP_003406.1
	ZNF268	NM_001165881.3		c.458-564G>A		intron	N/A	NP_001159353.1
	ZNF268	NM_001165882.3		c.209-564G>A		intron	N/A	NP_001159354.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF268	ENST00000536435.7	TSL:1 MANE Select	c.458-564G>A		intron	N/A	ENSP00000444412.3
	ZNF268	ENST00000228289.9	TSL:1	c.458-564G>A		intron	N/A	ENSP00000228289.5
	ENSG00000256825	ENST00000540096.2	TSL:2	c.1059-564G>A		intron	N/A	ENSP00000457704.2

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52149 AN: 151670 Hom.: 9392 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.0866

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.344 AC: 52188 AN: 151788 Hom.: 9400 Cov.: 32 AF XY: 0.338 AC XY: 25104 AN XY: 74170

African (AFR) AF: 0.414 AC: 17144 AN: 41402

American (AMR) AF: 0.278 AC: 4238 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1128 AN: 3468

East Asian (EAS) AF: 0.0870 AC: 450 AN: 5174

South Asian (SAS) AF: 0.280 AC: 1346 AN: 4806

European-Finnish (FIN) AF: 0.328 AC: 3456 AN: 10544

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23456 AN: 67840

Other (OTH) AF: 0.300 AC: 631 AN: 2106

Alfa AF: 0.350 Hom.: 1589

Bravo AF: 0.340

Asia WGS AF: 0.206 AC: 717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.35
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: rs7960480; hg19: chr12-133778166;