19-12581187-G-A

Position:

• chr19-12581187-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020714.3(ZNF490):​c.888C>T​(p.His296His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,613,530 control chromosomes in the GnomAD database, including 170,241 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 0.35 (11792 hom., cov: 32)
  • Exomes 𝑓: 0.45 (158449 hom.)
• Consequence: ZNF490 NM_020714.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708

Genes affected

ZNF490 (HGNC:23705): (zinc finger protein 490) 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. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=-0.708 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF490	NM_020714.3	c.888C>T	p.His296His	synonymous_variant	5/5	ENST00000311437.11	NP_065765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF490	ENST00000311437.11	c.888C>T	p.His296His	synonymous_variant	5/5	1	NM_020714.3	ENSP00000311521.6

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52623 AN: 151784 Hom.: 11787 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.0543

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.376

GnomAD3 exomes AF: 0.369 AC: 92790 AN: 251128 Hom.: 20762 AF XY: 0.381 AC XY: 51688 AN XY: 135764

Gnomad AFR exome AF: 0.0935

Gnomad AMR exome AF: 0.211

Gnomad ASJ exome AF: 0.557

Gnomad EAS exome AF: 0.0556

Gnomad SAS exome AF: 0.254

Gnomad FIN exome AF: 0.473

Gnomad NFE exome AF: 0.500

Gnomad OTH exome AF: 0.426

GnomAD4 exome AF: 0.450 AC: 657389 AN: 1461628 Hom.: 158449 Cov.: 52 AF XY: 0.447 AC XY: 325366 AN XY: 727098

Gnomad4 AFR exome AF: 0.0891

Gnomad4 AMR exome AF: 0.222

Gnomad4 ASJ exome AF: 0.563

Gnomad4 EAS exome AF: 0.0521

Gnomad4 SAS exome AF: 0.254

Gnomad4 FIN exome AF: 0.476

Gnomad4 NFE exome AF: 0.497

Gnomad4 OTH exome AF: 0.415

GnomAD4 genome AF: 0.346 AC: 52620 AN: 151902 Hom.: 11792 Cov.: 32 AF XY: 0.342 AC XY: 25358 AN XY: 74202

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.0542

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.374

Alfa AF: 0.470 Hom.: 41753

Bravo AF: 0.320

Asia WGS AF: 0.157 AC: 549 AN: 3478

EpiCase AF: 0.504

EpiControl AF: 0.500

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.2
DANN	Benign	0.46

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: rs3745651; hg19: chr19-12692001; COSMIC: COSV61008049; COSMIC: COSV61008049;