6-87157345-T-C

Variant names:

• chr6-87157345-T-C
• rs1925690
• NM_015021.3:c.168+1586T>C

Variant summary

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

The NM_015021.3(ZNF292):​c.168+1586T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.922 in 152,288 control chromosomes in the GnomAD database, including 64,937 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 0.92 (64937 hom., cov: 33)
• Consequence: ZNF292 NM_015021.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40
• Publications: 20 publications found

Genes affected

ZNF292 (HGNC:18410): (zinc finger protein 292) This gene encodes a growth hormone-dependent, zinc finger transcription factor that functions as a tumor suppressor. Naturally occurring mutations in this gene are associated with gastric cancer, colorectal cancer, and chronic lymphocytic leukemia. [provided by RefSeq, May 2017]

ZNF292 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen
• intellectual developmental disorder, autosomal dominant 64

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF292	NM_015021.3	c.168+1586T>C		intron_variant	Intron 1 of 7	ENST00000369577.8	NP_055836.1
ZNF292	NM_001351444.2	c.-398+1586T>C		intron_variant	Intron 1 of 8		NP_001338373.1
ZNF292	XM_047418459.1	c.-566+1586T>C		intron_variant	Intron 1 of 9		XP_047274415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF292	ENST00000369577.8	c.168+1586T>C		intron_variant	Intron 1 of 7	1	NM_015021.3	ENSP00000358590.3

Frequencies

GnomAD3 genomes AF: 0.922 AC: 140332 AN: 152170 Hom.: 64878 Cov.: 33

Gnomad AFR AF: 0.982

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.942

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.907

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

GnomAD4 genome AF: 0.922 AC: 140449 AN: 152288 Hom.: 64937 Cov.: 33 AF XY: 0.924 AC XY: 68777 AN XY: 74470

African (AFR) AF: 0.982 AC: 40809 AN: 41550

American (AMR) AF: 0.942 AC: 14424 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2995 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5186 AN: 5188

South Asian (SAS) AF: 0.926 AC: 4472 AN: 4830

European-Finnish (FIN) AF: 0.878 AC: 9313 AN: 10604

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60345 AN: 68016

Other (OTH) AF: 0.908 AC: 1920 AN: 2114

Alfa AF: 0.899 Hom.: 217298

Bravo AF: 0.930

Asia WGS AF: 0.969 AC: 3362 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.21
DANN	Benign	0.49
PhyloP100		-2.4
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: rs1925690; hg19: chr6-87867063;