rs2294120

Positions:

• chr8-144778182-A-G
• chr8-144778182-A-T

Variant summary

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

The NM_001286769.2(ZNF34):​c.34-18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 1,604,922 control chromosomes in the GnomAD database, including 174,472 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 0.38 (13140 hom., cov: 32)
  • Exomes 𝑓: 0.46 (161332 hom.)
• Consequence: ZNF34 NM_001286769.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.842

Genes affected

ZNF34 (HGNC:13098): (zinc finger protein 34) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF34	NM_001286769.2	c.34-18T>C		intron_variant		ENST00000429371.7	NP_001273698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF34	ENST00000429371.7	c.34-18T>C		intron_variant		1	NM_001286769.2	ENSP00000396894	P2

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57789 AN: 151990 Hom.: 13143 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.383

GnomAD3 exomes AF: 0.480 AC: 115068 AN: 239786 Hom.: 29411 AF XY: 0.485 AC XY: 63033 AN XY: 129956

Gnomad AFR exome AF: 0.111

Gnomad AMR exome AF: 0.537

Gnomad ASJ exome AF: 0.446

Gnomad EAS exome AF: 0.735

Gnomad SAS exome AF: 0.560

Gnomad FIN exome AF: 0.469

Gnomad NFE exome AF: 0.457

Gnomad OTH exome AF: 0.451

GnomAD4 exome AF: 0.464 AC: 673818 AN: 1452814 Hom.: 161332 Cov.: 49 AF XY: 0.468 AC XY: 337900 AN XY: 722094

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.528

Gnomad4 ASJ exome AF: 0.437

Gnomad4 EAS exome AF: 0.733

Gnomad4 SAS exome AF: 0.558

Gnomad4 FIN exome AF: 0.468

Gnomad4 NFE exome AF: 0.457

Gnomad4 OTH exome AF: 0.448

GnomAD4 genome AF: 0.380 AC: 57794 AN: 152108 Hom.: 13140 Cov.: 32 AF XY: 0.387 AC XY: 28741 AN XY: 74354

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.731

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.384

Alfa AF: 0.451 Hom.: 7032

Bravo AF: 0.370

Asia WGS AF: 0.602 AC: 2095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	8.2
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs2294120; hg19: chr8-146003567; COSMIC: COSV58638595;