rs2278418

Positions:

• chr19-51968532-T-A

Variant summary

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

The NM_021632.4(ZNF350):​c.238+46A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,544,874 control chromosomes in the GnomAD database, including 27,643 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 0.24 (4985 hom., cov: 31)
  • Exomes 𝑓: 0.17 (22658 hom.)
• Consequence: ZNF350 NM_021632.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF350	NM_021632.4	c.238+46A>T		intron_variant		ENST00000243644.9
ZNF350-AS1	NR_103847.1	n.103-7859T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF350	ENST00000243644.9	c.238+46A>T		intron_variant		1	NM_021632.4	P1
ZNF350-AS1	ENST00000595010.4	n.121-7859T>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35651 AN: 151832 Hom.: 4957 Cov.: 31

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.216

GnomAD3 exomes AF: 0.203 AC: 50950 AN: 250848 Hom.: 5646 AF XY: 0.201 AC XY: 27239 AN XY: 135564

Gnomad AFR exome AF: 0.380

Gnomad AMR exome AF: 0.177

Gnomad ASJ exome AF: 0.202

Gnomad EAS exome AF: 0.222

Gnomad SAS exome AF: 0.268

Gnomad FIN exome AF: 0.240

Gnomad NFE exome AF: 0.159

Gnomad OTH exome AF: 0.190

GnomAD4 exome AF: 0.172 AC: 239707 AN: 1392924 Hom.: 22658 Cov.: 23 AF XY: 0.174 AC XY: 121393 AN XY: 696762

Gnomad4 AFR exome AF: 0.378

Gnomad4 AMR exome AF: 0.183

Gnomad4 ASJ exome AF: 0.199

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.262

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.184

GnomAD4 genome AF: 0.235 AC: 35741 AN: 151950 Hom.: 4985 Cov.: 31 AF XY: 0.239 AC XY: 17781 AN XY: 74268

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.220

Alfa AF: 0.200 Hom.: 608

Bravo AF: 0.233

Asia WGS AF: 0.308 AC: 1070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.78
DANN	Benign	0.71

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: rs2278418; hg19: chr19-52471785; COSMIC: COSV54708593; COSMIC: COSV54708593;