4-145932013-A-G

Variant summary

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

The NM_001306215.2(ZNF827):c.43+6352T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.931 in 152,190 control chromosomes in the GnomAD database, including 66,056 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 0.93 (66056 hom., cov: 30)
• Consequence: ZNF827 NM_001306215.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241

Genes affected

ZNF827 (HGNC:27193): (zinc finger protein 827) Predicted to enable DNA binding activity and metal ion binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• 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/exons	MANE	UniProt
ZNF827	NM_001306215.2	c.43+6352T>C		intron_variant		ENST00000508784.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF827	ENST00000508784.6	c.43+6352T>C		intron_variant		1	NM_001306215.2

Frequencies

GnomAD3 genomes AF: 0.931 AC: 141515 AN: 152072 Hom.: 65994 Cov.: 30

Gnomad AFR AF: 0.978

Gnomad AMI AF: 0.869

Gnomad AMR AF: 0.916

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.982

Gnomad FIN AF: 0.960

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.897

Gnomad OTH AF: 0.907

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

GnomAD4 genome AF: 0.931 AC: 141637 AN: 152190 Hom.: 66056 Cov.: 30 AF XY: 0.934 AC XY: 69453 AN XY: 74386

Gnomad4 AFR AF: 0.978

Gnomad4 AMR AF: 0.916

Gnomad4 ASJ AF: 0.872

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.982

Gnomad4 FIN AF: 0.960

Gnomad4 NFE AF: 0.897

Gnomad4 OTH AF: 0.909

Alfa AF: 0.907 Hom.: 43852

Bravo AF: 0.929

Asia WGS AF: 0.986 AC: 3430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.9
Dann	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs2048161; hg19: chr4-146853165;