rs2278419

chr19-51968560-T-Cchr19-51968560-T-G

Variant summary

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

The NM_021632.4(ZNF350):c.238+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,608,078 control chromosomes in the GnomAD database, including 80,835 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 0.39 (13334 hom., cov: 31)
  • Exomes 𝑓: 0.29 (67501 hom.)
• Consequence: ZNF350 NM_021632.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756

Genes affected

ZNF350 (HGNC:16656): (zinc finger protein 350) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nuclear body. Part of transcription repressor complex. [provided by Alliance of Genome Resources, Apr 2022]

ZNF350-AS1 (HGNC:48598): (ZNF350 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF350	NM_021632.4	c.238+18A>G		intron_variant		ENST00000243644.9
ZNF350-AS1	NR_103847.1	n.103-7831T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF350	ENST00000243644.9	c.238+18A>G		intron_variant		1	NM_021632.4	P1
ZNF350-AS1	ENST00000595010.4	n.121-7831T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58536 AN: 151774 Hom.: 13282 Cov.: 31

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.370

GnomAD3 exomes AF: 0.332 AC: 83378 AN: 251244 Hom.: 15860 AF XY: 0.335 AC XY: 45522 AN XY: 135794

Gnomad AFR exome AF: 0.639

Gnomad AMR exome AF: 0.256

Gnomad ASJ exome AF: 0.307

Gnomad EAS exome AF: 0.286

Gnomad SAS exome AF: 0.533

Gnomad FIN exome AF: 0.334

Gnomad NFE exome AF: 0.267

Gnomad OTH exome AF: 0.306

GnomAD4 exome AF: 0.291 AC: 423535 AN: 1456184 Hom.: 67501 Cov.: 29 AF XY: 0.297 AC XY: 214959 AN XY: 724706

Gnomad4 AFR exome AF: 0.643

Gnomad4 AMR exome AF: 0.264

Gnomad4 ASJ exome AF: 0.303

Gnomad4 EAS exome AF: 0.289

Gnomad4 SAS exome AF: 0.520

Gnomad4 FIN exome AF: 0.326

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.313

GnomAD4 genome AF: 0.386 AC: 58649 AN: 151894 Hom.: 13334 Cov.: 31 AF XY: 0.391 AC XY: 29025 AN XY: 74234

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.375

Alfa AF: 0.312 Hom.: 2505

Bravo AF: 0.388

Asia WGS AF: 0.495 AC: 1719 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.0
Dann	Benign	0.44

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: rs2278419; hg19: chr19-52471813; COSMIC: COSV54708598; COSMIC: COSV54708598;