rs2239730

Variant names:

• chr11-6955944-G-C
• rs2239730
• NM_013250.4:c.967G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013250.4(ZNF215):​c.967G>C​(p.Val323Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,612,506 control chromosomes in the GnomAD database, including 37,006 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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 (4715 hom., cov: 33)
  • Exomes 𝑓: 0.20 (32291 hom.)
• Consequence: ZNF215 NM_013250.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 20 publications found

Genes affected

ZNF215 (HGNC:13007): (zinc finger protein 215) This gene is imprinted in a tissue-specific manner with preferential expression in the testis, and encodes a zinc finger protein that belongs to a family of zinc finger transcription factors. The encoded protein contains an N-terminal SRE-ZBP, Ctfin51, AW-1, and Number 18 (SCAN) domain, a kruppel-associated box A (KRABA) domain, and four C-terminal zinc finger domains. This gene is located within one of three regions on chromosome 11p15 associated with Beckwith-Wiedemann syndrome, called Beckwith-Wiedemann syndrome chromosome region-2 (BWSCR2), and is thought to play a role in the etiology of this disease. [provided by RefSeq, Aug 2017]

ZNF215 Gene-Disease associations (from GenCC):

• Beckwith-Wiedemann syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

LOC102724711 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0039271414).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013250.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF215	NM_013250.4	MANE Select	c.967G>C	p.Val323Leu	missense	Exon 7 of 7	NP_037382.2
	ZNF215	NM_001354853.2		c.967G>C	p.Val323Leu	missense	Exon 7 of 7	NP_001341782.1
	ZNF215	NM_001354855.2		c.289G>C	p.Val97Leu	missense	Exon 6 of 6	NP_001341784.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF215	ENST00000278319.10	TSL:1 MANE Select	c.967G>C	p.Val323Leu	missense	Exon 7 of 7	ENSP00000278319.5
	ZNF215	ENST00000529903.1	TSL:1	c.805+162G>C		intron	N/A	ENSP00000432306.1
	ZNF215	ENST00000414517.6	TSL:5	c.967G>C	p.Val323Leu	missense	Exon 6 of 6	ENSP00000393202.2

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36271 AN: 152000 Hom.: 4709 Cov.: 33

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.0810

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.228

GnomAD2 exomes AF: 0.189 AC: 47091 AN: 249142 AF XY: 0.184

Gnomad AFR exome AF: 0.343

Gnomad AMR exome AF: 0.112

Gnomad ASJ exome AF: 0.248

Gnomad EAS exome AF: 0.139

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.214

Gnomad OTH exome AF: 0.205

GnomAD4 exome AF: 0.205 AC: 299208 AN: 1460388 Hom.: 32291 Cov.: 37 AF XY: 0.201 AC XY: 145823 AN XY: 726446

African (AFR) AF: 0.338 AC: 11286 AN: 33348

American (AMR) AF: 0.121 AC: 5401 AN: 44506

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 6483 AN: 26080

East Asian (EAS) AF: 0.153 AC: 6076 AN: 39680

South Asian (SAS) AF: 0.0821 AC: 7049 AN: 85862

European-Finnish (FIN) AF: 0.230 AC: 12276 AN: 53336

Middle Eastern (MID) AF: 0.225 AC: 1296 AN: 5750

European-Non Finnish (NFE) AF: 0.213 AC: 236702 AN: 1111506

Other (OTH) AF: 0.210 AC: 12639 AN: 60320

GnomAD4 genome AF: 0.239 AC: 36303 AN: 152118 Hom.: 4715 Cov.: 33 AF XY: 0.237 AC XY: 17627 AN XY: 74362

African (AFR) AF: 0.333 AC: 13808 AN: 41482

American (AMR) AF: 0.176 AC: 2698 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 866 AN: 3472

East Asian (EAS) AF: 0.150 AC: 779 AN: 5180

South Asian (SAS) AF: 0.0818 AC: 395 AN: 4826

European-Finnish (FIN) AF: 0.230 AC: 2431 AN: 10568

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14525 AN: 67986

Other (OTH) AF: 0.226 AC: 477 AN: 2112

Alfa AF: 0.216 Hom.: 2823

Bravo AF: 0.243

TwinsUK AF: 0.222 AC: 823

ALSPAC AF: 0.209 AC: 807

ESP6500AA AF: 0.335 AC: 1472

ESP6500EA AF: 0.213 AC: 1831

ExAC AF: 0.193 AC: 23418

Asia WGS AF: 0.115 AC: 402 AN: 3478

EpiCase AF: 0.223

EpiControl AF: 0.221

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.8
DANN	Benign	0.81
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0021	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.4
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.041
Sift	Benign	0.25	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.011
MutPred		0.35		Loss of loop (P = 0.1242)
MPC		0.0059
ClinPred		0.0047	T
GERP RS		2.5
Varity_R		0.046
gMVP		0.042
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: rs2239730; hg19: chr11-6977175; COSMIC: COSV53491730;