5-179028746-A-G

Position:

• chr5-179028746-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136116.3(ZNF879):​c.256+619A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,990 control chromosomes in the GnomAD database, including 29,072 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 0.62 (29072 hom., cov: 32)
• Consequence: ZNF879 NM_001136116.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.73

Genes affected

ZNF879 (HGNC:37273): (zinc finger protein 879) This gene encodes a kruppel-associated box-containing zinc finger protein (KRAB-ZFP). The encoded protein contains an N-terminal kruppel-associated box (KRAB) domain and thirteen C-terminal C2H2-type zinc finger domains. The KRAB-ZFPs represent the largest family of mammalian transcriptional repressors, which function through the recruitment of the nuclear co-factor KRAB-Associated Protein 1 (KAP1), to engage histone modifiers and induce heterochromatin formation. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF879	NM_001136116.3	c.256+619A>G		intron_variant		ENST00000444149.7	NP_001129588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF879	ENST00000444149.7	c.256+619A>G		intron_variant		1	NM_001136116.3	ENSP00000414887.2
ZNF879	ENST00000522442.1	c.256+619A>G		intron_variant		4		ENSP00000428477.1
ZNF879	ENST00000519896.5	c.290+619A>G		intron_variant		4		ENSP00000430047.1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93472 AN: 151872 Hom.: 29035 Cov.: 32

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.616 AC: 93562 AN: 151990 Hom.: 29072 Cov.: 32 AF XY: 0.619 AC XY: 45975 AN XY: 74264

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.843

Gnomad4 SAS AF: 0.814

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.665

Alfa AF: 0.600 Hom.: 12417

Bravo AF: 0.620

Asia WGS AF: 0.819 AC: 2847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.021
DANN	Benign	0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4105175; hg19: chr5-178455747;