4-145873469-T-C

Variant names:

• chr4-145873469-T-C
• rs4547811
• NM_001306215.2:c.1748-2991A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 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.1748-2991A>G		intron	N/A	NP_001293144.1	Q17R98-1
	ZNF827	NM_001410850.1		c.1748-2991A>G		intron	N/A	NP_001397779.1	H0Y9M2
	ZNF827	NM_178835.5		c.1748-2991A>G		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.1748-2991A>G		intron	N/A	ENSP00000421863.1	Q17R98-1
	ZNF827	ENST00000513320.5	TSL:1	c.698-2991A>G		intron	N/A	ENSP00000423130.1	G5E9Z1
	ZNF827	ENST00000503462.3	TSL:4	c.1748-2991A>G		intron	N/A	ENSP00000424541.2	H0Y9M2

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

African (AFR) AF: 0.189 AC: 7858 AN: 41510

American (AMR) AF: 0.336 AC: 5129 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 452 AN: 3472

East Asian (EAS) AF: 0.431 AC: 2227 AN: 5162

South Asian (SAS) AF: 0.261 AC: 1259 AN: 4824

European-Finnish (FIN) AF: 0.170 AC: 1803 AN: 10584

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11951 AN: 67992

Other (OTH) AF: 0.208 AC: 440 AN: 2114

Alfa AF: 0.190 Hom.: 9401

Bravo AF: 0.219

Asia WGS AF: 0.317 AC: 1103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.83
PhyloP100		-0.62
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: rs4547811; hg19: chr4-146794621;