rs2595500

Variant names:

• chr11-6941934-A-G
• rs2595500
• NM_013250.4:c.483+281A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_013250.4(ZNF215):​c.483+281A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,226 control chromosomes in the GnomAD database, including 2,254 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 0.16 (2254 hom., cov: 32)
• Consequence: ZNF215 NM_013250.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 8 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)

LOC107984019 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF215	NM_013250.4	c.483+281A>G		intron_variant	Intron 4 of 6	ENST00000278319.10	NP_037382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF215	ENST00000278319.10	c.483+281A>G		intron_variant	Intron 4 of 6	1	NM_013250.4	ENSP00000278319.5

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24426 AN: 152108 Hom.: 2256 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.0516

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.168

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.160 AC: 24429 AN: 152226 Hom.: 2254 Cov.: 32 AF XY: 0.156 AC XY: 11625 AN XY: 74432

African (AFR) AF: 0.106 AC: 4415 AN: 41558

American (AMR) AF: 0.158 AC: 2421 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 749 AN: 3470

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5190

South Asian (SAS) AF: 0.0521 AC: 251 AN: 4818

European-Finnish (FIN) AF: 0.164 AC: 1735 AN: 10600

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

European-Non Finnish (NFE) AF: 0.209 AC: 14216 AN: 67982

Other (OTH) AF: 0.166 AC: 350 AN: 2108

Alfa AF: 0.179 Hom.: 1895

Bravo AF: 0.159

Asia WGS AF: 0.0400 AC: 143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.82
PhyloP100		1.3
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: rs2595500; hg19: chr11-6963165;