4-145823489-T-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_001306215.2(ZNF827):c.2316A>T(p.Pro772=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,604,830 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (80 hom.)
• Consequence: ZNF827 NM_001306215.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.165

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 4-145823489-T-A is Benign according to our data. Variant chr4-145823489-T-A is described in ClinVar as [Benign]. Clinvar id is 779878.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.165 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00201 (288/143478) while in subpopulation EAS AF= 0.0488 (241/4934). AF 95% confidence interval is 0.0438. There are 11 homozygotes in gnomad4. There are 151 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 286 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF827	NM_001306215.2	c.2316A>T	p.Pro772=	synonymous_variant	8/15	ENST00000508784.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF827	ENST00000508784.6	c.2316A>T	p.Pro772=	synonymous_variant	8/15	1	NM_001306215.2

Frequencies

GnomAD3 genomes AF: 0.00199 AC: 286 AN: 143378 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.000473

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000592

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0485

Gnomad SAS AF: 0.00194

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00507

GnomAD3 exomes AF: 0.00342 AC: 861 AN: 251464 Hom.: 18 AF XY: 0.00327 AC XY: 445 AN XY: 135902

Gnomad AFR exome AF: 0.000861

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0439

Gnomad SAS exome AF: 0.000588

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00156 AC: 2283 AN: 1461352 Hom.: 80 Cov.: 33 AF XY: 0.00146 AC XY: 1065 AN XY: 726994

Gnomad4 AFR exome AF: 0.000359

Gnomad4 AMR exome AF: 0.0000671

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0457

Gnomad4 SAS exome AF: 0.000684

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000162

Gnomad4 OTH exome AF: 0.00625

GnomAD4 genome AF: 0.00201 AC: 288 AN: 143478 Hom.: 11 Cov.: 32 AF XY: 0.00218 AC XY: 151 AN XY: 69182

Gnomad4 AFR AF: 0.000472

Gnomad4 AMR AF: 0.000591

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0488

Gnomad4 SAS AF: 0.00216

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000150

Gnomad4 OTH AF: 0.00501

Alfa AF: 0.000769 Hom.: 0

Bravo AF: 0.00198

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 30, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
Cadd	Benign	7.6
Dann	Benign	0.76

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: rs74731224; hg19: chr4-146744641; COSMIC: COSV65230932;