Variant chrX-2490618-G-A 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_001171136.2(ZBED1):c.102C>T(p.Asn34=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000571 in 1,613,980 control chromosomes in the GnomAD database, including 3 homozygotes. There are 394 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. N34N) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., 203 hem., cov: 32)

Exomes 𝑓: 0.00031 ( 2 hom. 191 hem. )

Consequence

ZBED1
NM_001171136.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.10

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant X-2490618-G-A is Benign according to our data. Variant chrX-2490618-G-A is described in ClinVar as [Benign]. Clinvar id is 787150.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.1 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 203 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZBED1	NM_001171136.2 linkuse as main transcript	c.102C>T	p.Asn34=	synonymous_variant	2/2	ENST00000652001.1
DHRSX	NM_145177.3 linkuse as main transcript	c.109+10199C>T		intron_variant		ENST00000334651.11
ZBED1	NM_001171135.2 linkuse as main transcript	c.102C>T	p.Asn34=	synonymous_variant	2/2
ZBED1	NM_004729.4 linkuse as main transcript	c.102C>T	p.Asn34=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBED1	ENST00000652001.1 linkuse as main transcript	c.102C>T	p.Asn34=	synonymous_variant	2/2		NM_001171136.2	P1
DHRSX	ENST00000334651.11 linkuse as main transcript	c.109+10199C>T		intron_variant		1	NM_145177.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00308

AC:

468

AN:

152190

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

203

AN XY:

74344

show subpopulations

Gnomad AFR

AF:

0.0108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000784

AC:

197

AN:

251180

Hom.:

AF XY:

0.000582

AC XY:

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.0112

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000309

AC:

451

AN:

1461672

Hom.:

Cov.:

AF XY:

0.000263

AC XY:

191

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.0108

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.000845

GnomAD4 genome

AF:

0.00309

AC:

470

AN:

152308

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

203

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0108

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Bravo

AF:

0.00349

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

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.0

DANN

Benign

0.76

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