19-37556173-A-G

Position:

• chr19-37556173-A-G

Variant summary

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

The NR_038248.1(ZNF571-AS1):​n.337+5182A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 697,602 control chromosomes in the GnomAD database, including 25,592 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 0.25 (5584 hom., cov: 32)
  • Exomes 𝑓: 0.24 (20008 hom.)
• Consequence: ZNF571-AS1 NR_038248.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131

Genes affected

ZNF571-AS1 (HGNC:44324): (ZNF571 antisense RNA 1)

ZNF540 (HGNC:25331): (zinc finger protein 540) Enables translation repressor activity, mRNA regulatory element binding. Involved in negative regulation of transcription, DNA-templated and negative regulation of translation. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF571 (HGNC:25000): (zinc finger protein 571) 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 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF571-AS1	NR_038248.1	n.337+5182A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF571-AS1	ENST00000585578.5	n.209+7018A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38529 AN: 151900 Hom.: 5577 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.248

GnomAD3 exomes AF: 0.269 AC: 35464 AN: 131692 Hom.: 5807 AF XY: 0.267 AC XY: 19160 AN XY: 71746

Gnomad AFR exome AF: 0.335

Gnomad AMR exome AF: 0.289

Gnomad ASJ exome AF: 0.222

Gnomad EAS exome AF: 0.634

Gnomad SAS exome AF: 0.304

Gnomad FIN exome AF: 0.225

Gnomad NFE exome AF: 0.178

Gnomad OTH exome AF: 0.216

GnomAD4 exome AF: 0.240 AC: 130884 AN: 545584 Hom.: 20008 Cov.: 0 AF XY: 0.240 AC XY: 70806 AN XY: 294916

Gnomad4 AFR exome AF: 0.331

Gnomad4 AMR exome AF: 0.284

Gnomad4 ASJ exome AF: 0.223

Gnomad4 EAS exome AF: 0.668

Gnomad4 SAS exome AF: 0.304

Gnomad4 FIN exome AF: 0.217

Gnomad4 NFE exome AF: 0.179

Gnomad4 OTH exome AF: 0.223

GnomAD4 genome AF: 0.254 AC: 38554 AN: 152018 Hom.: 5584 Cov.: 32 AF XY: 0.258 AC XY: 19169 AN XY: 74292

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.245

Alfa AF: 0.210 Hom.: 704

Bravo AF: 0.259

Asia WGS AF: 0.433 AC: 1504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.89

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: rs10420268; hg19: chr19-38047075; COSMIC: COSV73897537;