rs2780231

chr20-46507805-C-T

Variant summary

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

The NM_001353824.2(ZNF334):c.22-3065G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,066 control chromosomes in the GnomAD database, including 18,260 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 0.49 (18260 hom., cov: 33)
• Consequence: ZNF334 NM_001353824.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140

Genes affected

ZNF334 (HGNC:15806): (zinc finger protein 334) This gene encodes a member of the C2H2 zinc finger family. The encoded protein contains a Krueppel-associated box, fourteen C2H2 zinc finger domains, and four C2H2-type/integrase DNA-binding domains. Decreased expression of this gene may be a marker for rheumatoid arthritis. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF334	NM_001353824.2	c.22-3065G>A		intron_variant		ENST00000692313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF334	ENST00000692313.1	c.22-3065G>A		intron_variant			NM_001353824.2	P2

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74164 AN: 151948 Hom.: 18213 Cov.: 33

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.488 AC: 74265 AN: 152066 Hom.: 18260 Cov.: 33 AF XY: 0.489 AC XY: 36350 AN XY: 74322

Gnomad4 AFR AF: 0.503

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.493

Gnomad4 OTH AF: 0.490

Alfa AF: 0.492 Hom.: 7221

Bravo AF: 0.486

Asia WGS AF: 0.488 AC: 1700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.2
Dann	Benign	0.63

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: rs2780231; hg19: chr20-45136444; COSMIC: COSV61619389; COSMIC: COSV61619389;