rs7247513

Positions:

• chr19-12580371-C-T

Variant summary

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

The ENST00000311437.11(ZNF490):​c.*114G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,478,468 control chromosomes in the GnomAD database, including 313,605 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 0.58 (26582 hom., cov: 32)
  • Exomes 𝑓: 0.65 (287023 hom.)
• Consequence: ZNF490 ENST00000311437.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.24

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF490	NM_020714.3	c.*114G>A		3_prime_UTR_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.*114G>A		3_prime_UTR_variant	5/5	1	NM_020714.3	ENSP00000311521	P1

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87397 AN: 151896 Hom.: 26559 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.607

GnomAD4 exome AF: 0.649 AC: 860306 AN: 1326454 Hom.: 287023 Cov.: 42 AF XY: 0.645 AC XY: 417646 AN XY: 647238

Gnomad4 AFR exome AF: 0.423

Gnomad4 AMR exome AF: 0.496

Gnomad4 ASJ exome AF: 0.777

Gnomad4 EAS exome AF: 0.216

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.627

Gnomad4 NFE exome AF: 0.687

Gnomad4 OTH exome AF: 0.618

GnomAD4 genome AF: 0.575 AC: 87460 AN: 152014 Hom.: 26582 Cov.: 32 AF XY: 0.565 AC XY: 41973 AN XY: 74310

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.768

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.689

Gnomad4 OTH AF: 0.612

Alfa AF: 0.663 Hom.: 63045

Bravo AF: 0.563

Asia WGS AF: 0.327 AC: 1143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.88

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: rs7247513; hg19: chr19-12691185; COSMIC: COSV61008065; COSMIC: COSV61008065;