4-145873469-T-C

Position:

• chr4-145873469-T-C

Variant summary

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

The NM_001306215.2(ZNF827):​c.1748-2991A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,140 control chromosomes in the GnomAD database, including 3,622 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 0.21 (3622 hom., cov: 31)
• Consequence: ZNF827 NM_001306215.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.616

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF827	NM_001306215.2	c.1748-2991A>G		intron_variant		ENST00000508784.6	NP_001293144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF827	ENST00000508784.6	c.1748-2991A>G		intron_variant		1	NM_001306215.2	ENSP00000421863

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31198 AN: 152020 Hom.: 3613 Cov.: 31

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0661

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.205 AC: 31232 AN: 152140 Hom.: 3622 Cov.: 31 AF XY: 0.211 AC XY: 15718 AN XY: 74402

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.208

Alfa AF: 0.183 Hom.: 5230

Bravo AF: 0.219

Asia WGS AF: 0.317 AC: 1103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.83

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: rs4547811; hg19: chr4-146794621;