rs7960480

Positions:

• chr12-133201580-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF268	NM_003415.3	c.458-564G>A		intron_variant		ENST00000536435.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF268	ENST00000536435.7	c.458-564G>A		intron_variant		1	NM_003415.3	P1

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

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.0870

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.300

Alfa AF: 0.349 Hom.: 1522

Bravo AF: 0.340

Asia WGS AF: 0.206 AC: 717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs7960480; hg19: chr12-133778166;