4-145816831-A-T

Variant names:

• chr4-145816831-A-T
• rs878451
• NM_001306215.2:c.2383+6591T>A

Variant summary

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

The NM_001306215.2(ZNF827):​c.2383+6591T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,126 control chromosomes in the GnomAD database, including 6,914 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 0.29 (6914 hom., cov: 33)
• Consequence: ZNF827 NM_001306215.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138
• Publications: 2 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001306215.2. 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
	ZNF827	NM_001306215.2	MANE Select	c.2383+6591T>A		intron	N/A	NP_001293144.1	Q17R98-1
	ZNF827	NM_001410850.1		c.2383+6591T>A		intron	N/A	NP_001397779.1	H0Y9M2
	ZNF827	NM_178835.5		c.2383+6591T>A		intron	N/A	NP_849157.2	Q17R98-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF827	ENST00000508784.6	TSL:1 MANE Select	c.2383+6591T>A		intron	N/A	ENSP00000421863.1	Q17R98-1
	ZNF827	ENST00000513320.5	TSL:1	c.1333+6591T>A		intron	N/A	ENSP00000423130.1	G5E9Z1
	ZNF827	ENST00000503462.3	TSL:4	c.2383+6591T>A		intron	N/A	ENSP00000424541.2	H0Y9M2

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44669 AN: 152010 Hom.: 6909 Cov.: 33

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.0778

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.294 AC: 44714 AN: 152126 Hom.: 6914 Cov.: 33 AF XY: 0.285 AC XY: 21194 AN XY: 74354

African (AFR) AF: 0.332 AC: 13769 AN: 41500

American (AMR) AF: 0.238 AC: 3636 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1232 AN: 3470

East Asian (EAS) AF: 0.0782 AC: 405 AN: 5182

South Asian (SAS) AF: 0.239 AC: 1148 AN: 4812

European-Finnish (FIN) AF: 0.228 AC: 2414 AN: 10582

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21065 AN: 67970

Other (OTH) AF: 0.292 AC: 615 AN: 2108

Alfa AF: 0.164 Hom.: 309

Bravo AF: 0.297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	13
DANN	Benign	0.68
PhyloP100		0.14
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: rs878451; hg19: chr4-146737983;