Variant 1-200407480-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001281293.2(ZNF281):c.2226A>C(p.Gly742Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00724 in 1,614,104 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0074 ( 40 hom. )

Consequence

ZNF281
NM_001281293.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0500

Variant links:

Genes affected

ZNF281 (HGNC:13075): (zinc finger protein 281) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of gene expression; negative regulation of transcription by RNA polymerase II; and positive regulation of transcription, DNA-templated. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF281 links:

ENSG00000230623 (HGNC:):

ENSG00000230623 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 1-200407480-T-G is Benign according to our data. Variant chr1-200407480-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2639714.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.05 with no splicing effect.

BS2

High AC in GnomAd4 at 877 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF281	NM_001281293.2 linkuse as main transcript	c.2226A>C	p.Gly742Gly	synonymous_variant	2/2	ENST00000367353.2	NP_001268222.1	Q9Y2X9-1
ZNF281	NM_012482.5 linkuse as main transcript	c.2226A>C	p.Gly742Gly	synonymous_variant	2/2		NP_036614.1	Q9Y2X9-1
ZNF281	NM_001281294.2 linkuse as main transcript	c.2118A>C	p.Gly706Gly	synonymous_variant	3/3		NP_001268223.1	Q9Y2X9-2B3KMX4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF281	ENST00000367353.2 linkuse as main transcript	c.2226A>C	p.Gly742Gly	synonymous_variant	2/2	1	NM_001281293.2	ENSP00000356322.1	Q9Y2X9-1
ZNF281	ENST00000294740.3 linkuse as main transcript	c.2226A>C	p.Gly742Gly	synonymous_variant	2/2	1		ENSP00000294740.2	Q9Y2X9-1
ZNF281	ENST00000367352.3 linkuse as main transcript	c.2118A>C	p.Gly706Gly	synonymous_variant	3/3	2		ENSP00000356321.3	Q9Y2X9-2
ENSG00000230623	ENST00000637430.1 linkuse as main transcript	n.484+43952T>G		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00575

AC:

875

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0146

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00834

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00521

AC:

1309

AN:

251462

Hom.:

AF XY:

0.00506

AC XY:

688

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00240

Gnomad AMR exome

AF:

0.00228

Gnomad ASJ exome

AF:

0.00576

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.0137

Gnomad NFE exome

AF:

0.00696

Gnomad OTH exome

AF:

0.00521

GnomAD4 exome

AF:

0.00739

AC:

10802

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00722

AC XY:

5253

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00155

Gnomad4 AMR exome

AF:

0.00226

Gnomad4 ASJ exome

AF:

0.00451

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000394

Gnomad4 FIN exome

AF:

0.0120

Gnomad4 NFE exome

AF:

0.00858

Gnomad4 OTH exome

AF:

0.00515

GnomAD4 genome

AF:

0.00576

AC:

877

AN:

152224

Hom.:

Cov.:

AF XY:

0.00570

AC XY:

424

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0146

Gnomad4 NFE

AF:

0.00834

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00747

Hom.:

Bravo

AF:

0.00462

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

ZNF281: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.2

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over