rs2278418

Variant names:

• chr19-51968532-T-A
• rs2278418
• NM_021632.4:c.238+46A>T

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+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
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 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+46A>T		intron	N/A	NP_067645.3
	ZNF350-AS1	NR_103847.1		n.103-7859T>A		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+46A>T		intron	N/A	ENSP00000243644.3	Q9GZX5
	ZNF350-AS1	ENST00000595010.5	TSL:1	n.125-7859T>A		intron	N/A
	ZNF350	ENST00000853589.1		c.238+46A>T		intron	N/A	ENSP00000523648.1

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

GnomAD2 exomes AF: 0.203 AC: 50950 AN: 250848 AF XY: 0.201

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 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

African (AFR) AF: 0.378 AC: 12059 AN: 31898

American (AMR) AF: 0.183 AC: 8150 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 5114 AN: 25682

East Asian (EAS) AF: 0.229 AC: 9010 AN: 39326

South Asian (SAS) AF: 0.262 AC: 22227 AN: 84710

European-Finnish (FIN) AF: 0.231 AC: 12311 AN: 53228

Middle Eastern (MID) AF: 0.163 AC: 922 AN: 5648

European-Non Finnish (NFE) AF: 0.152 AC: 159241 AN: 1049740

Other (OTH) AF: 0.184 AC: 10673 AN: 58052

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

African (AFR) AF: 0.379 AC: 15668 AN: 41392

American (AMR) AF: 0.189 AC: 2884 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 674 AN: 3468

East Asian (EAS) AF: 0.222 AC: 1142 AN: 5152

South Asian (SAS) AF: 0.284 AC: 1363 AN: 4806

European-Finnish (FIN) AF: 0.252 AC: 2661 AN: 10572

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10715 AN: 67970

Other (OTH) AF: 0.220 AC: 464 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.78
DANN	Benign	0.71
PhyloP100		-0.61
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: rs2278418; hg19: chr19-52471785; COSMIC: COSV54708593; COSMIC: COSV54708593;