chr11-6960257-A-G

Variant names:

• chr11-6960257-A-G
• rs2638094
• ENST00000529903.1:c.805+4475A>G

Variant summary

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

The ENST00000529903.1(ZNF215):​c.805+4475A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,154 control chromosomes in the GnomAD database, including 2,163 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 (2163 hom., cov: 32)
• Consequence: ZNF215 ENST00000529903.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• Publications: 5 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 (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000529903.1. 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_001354854.1		c.805+4475A>G		intron	N/A	NP_001341783.1
	ZNF215	NR_149005.2		n.1433+4475A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF215	ENST00000529903.1	TSL:1	c.805+4475A>G		intron	N/A	ENSP00000432306.1
	ZNF215	ENST00000610573.4	TSL:5	c.805+4475A>G		intron	N/A	ENSP00000484674.1
	ZNF215	ENST00000636097.1	TSL:5	n.*126+4475A>G		intron	N/A	ENSP00000490414.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23820 AN: 152036 Hom.: 2164 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0499

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.157 AC: 23822 AN: 152154 Hom.: 2163 Cov.: 32 AF XY: 0.153 AC XY: 11368 AN XY: 74390

African (AFR) AF: 0.102 AC: 4226 AN: 41510

American (AMR) AF: 0.150 AC: 2295 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 805 AN: 3470

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5188

South Asian (SAS) AF: 0.0508 AC: 245 AN: 4826

European-Finnish (FIN) AF: 0.163 AC: 1727 AN: 10592

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13900 AN: 67982

Other (OTH) AF: 0.163 AC: 345 AN: 2114

Alfa AF: 0.184 Hom.: 1404

Bravo AF: 0.154

Asia WGS AF: 0.0350 AC: 124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.4
DANN	Benign	0.67
PhyloP100		-0.054
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2638094; hg19: chr11-6981488;