Variant chrX-2489886-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001171136.2(ZBED1):c.834G>A(p.Ala278=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00327 in 1,613,834 control chromosomes in the GnomAD database, including 138 homozygotes. There are 2,311 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. A278A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.017 ( 83 hom., 1237 hem., cov: 33)

Exomes 𝑓: 0.0018 ( 55 hom. 1074 hem. )

Consequence

ZBED1
NM_001171136.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.417

Variant links:

Genes affected

ZBED1 (HGNC:447): (zinc finger BED-type containing 1) This gene is located in the pseudoautosomal region 1 (PAR1) of X and Y chromosomes. It was earlier identified as a gene with similarity to Ac transposable elements, however, was found not to have transposase activity. Later studies show that this gene product is localized in the nucleus and functions as a transcription factor. It binds to DNA elements found in the promoter regions of several genes related to cell proliferation, such as histone H1, hence may have a role in regulating genes related to cell proliferation. Alternatively spliced transcript variants with different 5' untranslated region have been found for this gene. [provided by RefSeq, Jan 2010]

ZBED1 links:

DHRSX (HGNC:18399): (dehydrogenase/reductase X-linked) Predicted to enable oxidoreductase activity. Involved in positive regulation of autophagy. Located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

DHRSX links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant X-2489886-C-T is Benign according to our data. Variant chrX-2489886-C-T is described in ClinVar as [Benign]. Clinvar id is 777779.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.417 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZBED1	NM_001171136.2 linkuse as main transcript	c.834G>A	p.Ala278=	synonymous_variant	2/2	ENST00000652001.1
DHRSX	NM_145177.3 linkuse as main transcript	c.109+10931G>A		intron_variant		ENST00000334651.11
ZBED1	NM_001171135.2 linkuse as main transcript	c.834G>A	p.Ala278=	synonymous_variant	2/2
ZBED1	NM_004729.4 linkuse as main transcript	c.834G>A	p.Ala278=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBED1	ENST00000652001.1 linkuse as main transcript	c.834G>A	p.Ala278=	synonymous_variant	2/2		NM_001171136.2	P1
DHRSX	ENST00000334651.11 linkuse as main transcript	c.109+10931G>A		intron_variant		1	NM_145177.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0174

AC:

2644

AN:

152222

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

1232

AN XY:

74362

show subpopulations

Gnomad AFR

AF:

0.0593

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00473

AC:

1187

AN:

251066

Hom.:

AF XY:

0.00336

AC XY:

456

AN XY:

135734

show subpopulations

Gnomad AFR exome

AF:

0.0631

Gnomad AMR exome

AF:

0.00364

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00180

AC:

2624

AN:

1461494

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

1074

AN XY:

727066

show subpopulations

Gnomad4 AFR exome

AF:

0.0605

Gnomad4 AMR exome

AF:

0.00396

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000132

Gnomad4 OTH exome

AF:

0.00412

GnomAD4 genome

AF:

0.0174

AC:

2651

AN:

152340

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

1237

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0593

Gnomad4 AMR

AF:

0.00915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.0128

Bravo

AF:

0.0198

EpiCase

AF:

0.000218

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.32

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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