Variant chr17-79779392-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_005189.3(CBX2):c.147C>T(p.Ile49=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0239 in 1,613,810 control chromosomes in the GnomAD database, including 539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 53 hom., cov: 33)

Exomes 𝑓: 0.024 ( 486 hom. )

Consequence

CBX2
NM_005189.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0500

Variant links:

Genes affected

CBX2 (HGNC:1552): (chromobox 2) This gene encodes a component of the polycomb multiprotein complex, which is required to maintain the transcriptionally repressive state of many genes throughout development via chromatin remodeling and modification of histones. Disruption of this gene in mice results in male-to-female gonadal sex reversal. Mutations in this gene are also associated with gonadal dysgenesis in humans. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Mar 2010]

CBX2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 17-79779392-C-T is Benign according to our data. Variant chr17-79779392-C-T is described in ClinVar as [Benign]. Clinvar id is 1614331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-79779392-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.05 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0191 (2909/152290) while in subpopulation NFE AF= 0.0277 (1883/68012). AF 95% confidence interval is 0.0266. There are 53 homozygotes in gnomad4. There are 1406 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 53 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBX2	NM_005189.3 linkuse as main transcript	c.147C>T	p.Ile49=	synonymous_variant	3/5	ENST00000310942.9	NP_005180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBX2	ENST00000310942.9 linkuse as main transcript	c.147C>T	p.Ile49=	synonymous_variant	3/5	1	NM_005189.3	ENSP00000308750	P1	Q14781-1
CBX2	ENST00000269399.5 linkuse as main transcript	c.147C>T	p.Ile49=	synonymous_variant	3/4	1		ENSP00000269399		Q14781-2
CBX2	ENST00000571484.1 linkuse as main transcript	n.220C>T		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes

AF:

0.0191

AC:

2910

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00388

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0253

Gnomad ASJ

AF:

0.0259

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.0200

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0277

Gnomad OTH

AF:

0.0421

GnomAD3 exomes

AF:

0.0216

AC:

5399

AN:

250212

Hom.:

AF XY:

0.0226

AC XY:

3065

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.00297

Gnomad AMR exome

AF:

0.0193

Gnomad ASJ exome

AF:

0.0258

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0152

Gnomad FIN exome

AF:

0.0185

Gnomad NFE exome

AF:

0.0299

Gnomad OTH exome

AF:

0.0298

GnomAD4 exome

AF:

0.0244

AC:

35685

AN:

1461520

Hom.:

486

Cov.:

AF XY:

0.0244

AC XY:

17748

AN XY:

727058

show subpopulations

Gnomad4 AFR exome

AF:

0.00406

Gnomad4 AMR exome

AF:

0.0208

Gnomad4 ASJ exome

AF:

0.0236

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0155

Gnomad4 FIN exome

AF:

0.0191

Gnomad4 NFE exome

AF:

0.0268

Gnomad4 OTH exome

AF:

0.0258

GnomAD4 genome

AF:

0.0191

AC:

2909

AN:

152290

Hom.:

Cov.:

AF XY:

0.0189

AC XY:

1406

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00387

Gnomad4 AMR

AF:

0.0252

Gnomad4 ASJ

AF:

0.0259

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0147

Gnomad4 FIN

AF:

0.0200

Gnomad4 NFE

AF:

0.0277

Gnomad4 OTH

AF:

0.0417

Alfa

AF:

0.0255

Hom.:

Bravo

AF:

0.0188

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0363

EpiControl

AF:

0.0341

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.89

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