11-6955757-A-T

Variant names:

• chr11-6955757-A-T
• rs2239731
• NM_013250.4:c.780A>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_013250.4(ZNF215):​c.780A>T​(p.Gly260Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 1,608,472 control chromosomes in the GnomAD database, including 438,913 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 0.68 (35528 hom., cov: 32)
  • Exomes 𝑓: 0.74 (403385 hom.)
• Consequence: ZNF215 NM_013250.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.723
• Publications: 17 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=0.723 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.781 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF215	NM_013250.4	MANE Select	c.780A>T	p.Gly260Gly	synonymous	Exon 7 of 7	NP_037382.2	Q9UL58-1
	ZNF215	NM_001354853.2		c.780A>T	p.Gly260Gly	synonymous	Exon 7 of 7	NP_001341782.1	Q9UL58-1
	ZNF215	NM_001354854.1		c.780A>T	p.Gly260Gly	synonymous	Exon 6 of 7	NP_001341783.1	Q9UL58-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF215	ENST00000278319.10	TSL:1 MANE Select	c.780A>T	p.Gly260Gly	synonymous	Exon 7 of 7	ENSP00000278319.5	Q9UL58-1
	ZNF215	ENST00000529903.1	TSL:1	c.780A>T	p.Gly260Gly	synonymous	Exon 5 of 6	ENSP00000432306.1	Q9UL58-2
	ZNF215	ENST00000921289.1		c.783A>T	p.Gly261Gly	synonymous	Exon 7 of 7	ENSP00000591348.1

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102573 AN: 151872 Hom.: 35516 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.685

GnomAD2 exomes AF: 0.739 AC: 181844 AN: 245972 AF XY: 0.746

Gnomad AFR exome AF: 0.482

Gnomad AMR exome AF: 0.814

Gnomad ASJ exome AF: 0.700

Gnomad EAS exome AF: 0.732

Gnomad FIN exome AF: 0.736

Gnomad NFE exome AF: 0.741

Gnomad OTH exome AF: 0.730

GnomAD4 exome AF: 0.743 AC: 1081469 AN: 1456482 Hom.: 403385 Cov.: 54 AF XY: 0.746 AC XY: 539986 AN XY: 724242

African (AFR) AF: 0.488 AC: 16166 AN: 33114

American (AMR) AF: 0.804 AC: 35027 AN: 43556

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 18104 AN: 25832

East Asian (EAS) AF: 0.738 AC: 29285 AN: 39662

South Asian (SAS) AF: 0.805 AC: 68104 AN: 84578

European-Finnish (FIN) AF: 0.735 AC: 39208 AN: 53320

Middle Eastern (MID) AF: 0.705 AC: 4044 AN: 5740

European-Non Finnish (NFE) AF: 0.745 AC: 827860 AN: 1110514

Other (OTH) AF: 0.726 AC: 43671 AN: 60166

GnomAD4 genome AF: 0.675 AC: 102616 AN: 151990 Hom.: 35528 Cov.: 32 AF XY: 0.677 AC XY: 50252 AN XY: 74272

African (AFR) AF: 0.494 AC: 20453 AN: 41430

American (AMR) AF: 0.750 AC: 11447 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2424 AN: 3472

East Asian (EAS) AF: 0.726 AC: 3746 AN: 5162

South Asian (SAS) AF: 0.802 AC: 3859 AN: 4810

European-Finnish (FIN) AF: 0.739 AC: 7802 AN: 10556

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.744 AC: 50603 AN: 67972

Other (OTH) AF: 0.688 AC: 1453 AN: 2112

Alfa AF: 0.712 Hom.: 10379

Bravo AF: 0.665

Asia WGS AF: 0.758 AC: 2635 AN: 3478

EpiCase AF: 0.735

EpiControl AF: 0.737

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.46
PhyloP100		0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2239731; hg19: chr11-6976988; COSMIC: COSV99549237;