Variant 1-200407966-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001281293.2(ZNF281):c.1740A>G(p.Pro580Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00339 in 1,614,218 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 69 hom. )

Consequence

ZNF281
NM_001281293.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.80

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-200407966-T-C is Benign according to our data. Variant chr1-200407966-T-C is described in ClinVar as [Benign]. Clinvar id is 711738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00248 (378/152348) while in subpopulation SAS AF= 0.0259 (125/4832). AF 95% confidence interval is 0.0222. There are 6 homozygotes in gnomad4. There are 210 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 378 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF281	NM_001281293.2 linkuse as main transcript	c.1740A>G	p.Pro580Pro	synonymous_variant	2/2	ENST00000367353.2	NP_001268222.1	Q9Y2X9-1
ZNF281	NM_012482.5 linkuse as main transcript	c.1740A>G	p.Pro580Pro	synonymous_variant	2/2		NP_036614.1	Q9Y2X9-1
ZNF281	NM_001281294.2 linkuse as main transcript	c.1632A>G	p.Pro544Pro	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.1740A>G	p.Pro580Pro	synonymous_variant	2/2	1	NM_001281293.2	ENSP00000356322.1	Q9Y2X9-1
ZNF281	ENST00000294740.3 linkuse as main transcript	c.1740A>G	p.Pro580Pro	synonymous_variant	2/2	1		ENSP00000294740.2	Q9Y2X9-1
ZNF281	ENST00000367352.3 linkuse as main transcript	c.1632A>G	p.Pro544Pro	synonymous_variant	3/3	2		ENSP00000356321.3	Q9Y2X9-2
ENSG00000230623	ENST00000637430.1 linkuse as main transcript	n.484+44438T>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00248

AC:

378

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0258

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.00187

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00537

AC:

1349

AN:

251294

Hom.:

AF XY:

0.00665

AC XY:

903

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.0120

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0274

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00235

Gnomad OTH exome

AF:

0.00880

GnomAD4 exome

AF:

0.00349

AC:

5100

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00435

AC XY:

3165

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.0116

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0282

Gnomad4 FIN exome

AF:

0.000412

Gnomad4 NFE exome

AF:

0.00150

Gnomad4 OTH exome

AF:

0.00575

GnomAD4 genome

AF:

0.00248

AC:

378

AN:

152348

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

210

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0259

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00187

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00285

Hom.:

Bravo

AF:

0.00199

Asia WGS

AF:

0.00953

AC:

AN:

3478

EpiCase

AF:

0.00294

EpiControl

AF:

0.00409

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.9

DANN

Benign

0.41

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