chr11-6932384-G-A

Position:

• chr11-6932384-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_013250.4(ZNF215):​c.112G>A​(p.Val38Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,614,090 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.011 (33 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (25 hom.)
• Consequence: ZNF215 NM_013250.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.308

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026695132).
• BP6: Variant 11-6932384-G-A is Benign according to our data. Variant chr11-6932384-G-A is described in ClinVar as [Benign]. Clinvar id is 787901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0106 (1619/152204) while in subpopulation AFR AF= 0.037 (1535/41528). AF 95% confidence interval is 0.0354. There are 33 homozygotes in gnomad4. There are 802 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF215	NM_013250.4	c.112G>A	p.Val38Ile	missense_variant	3/7	ENST00000278319.10	NP_037382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF215	ENST00000278319.10	c.112G>A	p.Val38Ile	missense_variant	3/7	1	NM_013250.4	ENSP00000278319.5

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1612 AN: 152086 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.0369

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00909

GnomAD3 exomes AF: 0.00274 AC: 688 AN: 251440 Hom.: 11 AF XY: 0.00199 AC XY: 271 AN XY: 135902

Gnomad AFR exome AF: 0.0378

Gnomad AMR exome AF: 0.00165

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000703

Gnomad OTH exome AF: 0.000651

GnomAD4 exome AF: 0.00113 AC: 1656 AN: 1461886 Hom.: 25 Cov.: 30 AF XY: 0.000954 AC XY: 694 AN XY: 727242

Gnomad4 AFR exome AF: 0.0397

Gnomad4 AMR exome AF: 0.00186

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000728

Gnomad4 OTH exome AF: 0.00238

GnomAD4 genome AF: 0.0106 AC: 1619 AN: 152204 Hom.: 33 Cov.: 32 AF XY: 0.0108 AC XY: 802 AN XY: 74416

Gnomad4 AFR AF: 0.0370

Gnomad4 AMR AF: 0.00379

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.00195 Hom.: 8

Bravo AF: 0.0125

ESP6500AA AF: 0.0384 AC: 169

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00343 AC: 416

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.27
DANN	Benign	0.55
DEOGEN2	Benign	0.0021	T;.;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.078	.;T;T;.
MetaRNN	Benign	0.0027	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.2	L;L;L;L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.38	N;.;N;N
REVEL	Benign	0.0090
Sift	Benign	1.0	T;.;T;T
Sift4G	Benign	0.83	T;T;T;T
Polyphen		0.0	B;.;B;.
Vest4		0.074
MVP		0.10
MPC		0.0063
ClinPred		0.0020	T
GERP RS		-1.6
Varity_R		0.016
gMVP		0.061

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: rs35111903; hg19: chr11-6953615; COSMIC: COSV99066437;