rs2278419

Variant names:

• chr19-51968560-T-C
• rs2278419
• NM_021632.4:c.238+18A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-51968560-T-C
• chr19-51968560-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021632.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF350	NM_021632.4	MANE Select	c.238+18A>G		intron	N/A	NP_067645.3
	ZNF350-AS1	NR_103847.1		n.103-7831T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF350	ENST00000243644.9	TSL:1 MANE Select	c.238+18A>G		intron	N/A	ENSP00000243644.3	Q9GZX5
	ZNF350-AS1	ENST00000595010.5	TSL:1	n.125-7831T>C		intron	N/A
	ZNF350	ENST00000853589.1		c.238+18A>G		intron	N/A	ENSP00000523648.1

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

GnomAD2 exomes AF: 0.332 AC: 83378 AN: 251244 AF XY: 0.335

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 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

African (AFR) AF: 0.643 AC: 21444 AN: 33344

American (AMR) AF: 0.264 AC: 11802 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 7915 AN: 26090

East Asian (EAS) AF: 0.289 AC: 11481 AN: 39662

South Asian (SAS) AF: 0.520 AC: 44804 AN: 86132

European-Finnish (FIN) AF: 0.326 AC: 17396 AN: 53388

Middle Eastern (MID) AF: 0.296 AC: 1704 AN: 5748

European-Non Finnish (NFE) AF: 0.260 AC: 288137 AN: 1106896

Other (OTH) AF: 0.313 AC: 18852 AN: 60224

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

African (AFR) AF: 0.632 AC: 26158 AN: 41396

American (AMR) AF: 0.294 AC: 4491 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1053 AN: 3470

East Asian (EAS) AF: 0.286 AC: 1469 AN: 5142

South Asian (SAS) AF: 0.547 AC: 2635 AN: 4816

European-Finnish (FIN) AF: 0.344 AC: 3621 AN: 10538

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 18016 AN: 67942

Other (OTH) AF: 0.375 AC: 792 AN: 2110

Alfa AF: 0.317 Hom.: 2649

Bravo AF: 0.388

Asia WGS AF: 0.495 AC: 1719 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.44
PhyloP100		-0.76
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: rs2278419; hg19: chr19-52471813; COSMIC: COSV54708598; COSMIC: COSV54708598;