rs3745651

Variant names:

• chr19-12581187-G-A
• rs3745651
• NM_020714.3:c.888C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-12581187-G-A
• chr19-12581187-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 34 publications found

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]

ENSG00000269693 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF490	NM_020714.3	c.888C>T	p.His296His	synonymous_variant	Exon 5 of 5	ENST00000311437.11	NP_065765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF490	ENST00000311437.11	c.888C>T	p.His296His	synonymous_variant	Exon 5 of 5	1	NM_020714.3	ENSP00000311521.6
ENSG00000269693	ENST00000593682.1	n.-214C>T		upstream_gene_variant		1		ENSP00000473043.1
ZNF490	ENST00000414906.5	n.*810C>T		downstream_gene_variant		3		ENSP00000402719.1

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

GnomAD2 exomes AF: 0.369 AC: 92790 AN: 251128 AF XY: 0.381

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 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

African (AFR) AF: 0.0891 AC: 2980 AN: 33462

American (AMR) AF: 0.222 AC: 9930 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 14722 AN: 26130

East Asian (EAS) AF: 0.0521 AC: 2069 AN: 39696

South Asian (SAS) AF: 0.254 AC: 21939 AN: 86246

European-Finnish (FIN) AF: 0.476 AC: 25417 AN: 53396

Middle Eastern (MID) AF: 0.476 AC: 2748 AN: 5768

European-Non Finnish (NFE) AF: 0.497 AC: 552543 AN: 1111862

Other (OTH) AF: 0.415 AC: 25041 AN: 60376

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

African (AFR) AF: 0.101 AC: 4176 AN: 41446

American (AMR) AF: 0.282 AC: 4302 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1950 AN: 3468

East Asian (EAS) AF: 0.0542 AC: 280 AN: 5162

South Asian (SAS) AF: 0.236 AC: 1137 AN: 4814

European-Finnish (FIN) AF: 0.485 AC: 5101 AN: 10518

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34295 AN: 67928

Other (OTH) AF: 0.374 AC: 789 AN: 2110

Alfa AF: 0.447 Hom.: 54994

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
PhyloP100		-0.71
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: rs3745651; hg19: chr19-12692001; COSMIC: COSV61008049; COSMIC: COSV61008049;