chr11-6941726-C-T

Variant names:

• chr11-6941726-C-T
• rs2857891
• NM_013250.4:c.483+73C>T

Variant summary

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

The NM_013250.4(ZNF215):​c.483+73C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,508,188 control chromosomes in the GnomAD database, including 28,650 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 (2259 hom., cov: 33)
  • Exomes 𝑓: 0.19 (26391 hom.)
• Consequence: ZNF215 NM_013250.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.443
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 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.483+73C>T		intron	N/A	NP_037382.2	Q9UL58-1
	ZNF215	NM_001354853.2		c.483+73C>T		intron	N/A	NP_001341782.1	Q9UL58-1
	ZNF215	NM_001354854.1		c.483+73C>T		intron	N/A	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.483+73C>T		intron	N/A	ENSP00000278319.5	Q9UL58-1
	ZNF215	ENST00000529903.1	TSL:1	c.483+73C>T		intron	N/A	ENSP00000432306.1	Q9UL58-2
	ZNF215	ENST00000921289.1		c.483+73C>T		intron	N/A	ENSP00000591348.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24433 AN: 152090 Hom.: 2261 Cov.: 33

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.0520

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.189 AC: 256025 AN: 1355980 Hom.: 26391 AF XY: 0.185 AC XY: 125193 AN XY: 675992

African (AFR) AF: 0.104 AC: 3203 AN: 30844

American (AMR) AF: 0.116 AC: 4699 AN: 40402

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 5344 AN: 24570

East Asian (EAS) AF: 0.00220 AC: 83 AN: 37742

South Asian (SAS) AF: 0.0598 AC: 4826 AN: 80748

European-Finnish (FIN) AF: 0.173 AC: 8654 AN: 50104

Middle Eastern (MID) AF: 0.198 AC: 1100 AN: 5554

European-Non Finnish (NFE) AF: 0.212 AC: 217796 AN: 1029484

Other (OTH) AF: 0.183 AC: 10320 AN: 56532

GnomAD4 genome AF: 0.161 AC: 24436 AN: 152208 Hom.: 2259 Cov.: 33 AF XY: 0.156 AC XY: 11641 AN XY: 74426

African (AFR) AF: 0.106 AC: 4418 AN: 41532

American (AMR) AF: 0.158 AC: 2419 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 749 AN: 3472

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5188

South Asian (SAS) AF: 0.0524 AC: 253 AN: 4824

European-Finnish (FIN) AF: 0.165 AC: 1745 AN: 10588

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

European-Non Finnish (NFE) AF: 0.209 AC: 14209 AN: 67990

Other (OTH) AF: 0.166 AC: 351 AN: 2114

Alfa AF: 0.188 Hom.: 7855

Bravo AF: 0.159

Asia WGS AF: 0.0430 AC: 154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	13
DANN	Benign	0.70
PhyloP100		0.44
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: rs2857891; hg19: chr11-6962957;