Variant chr13-27556336-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_153371.4(LNX2):c.1446C>T(p.Thr482=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0025 in 1,613,920 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 27 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 22 hom. )

Consequence

LNX2
NM_153371.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.26

Variant links:

Genes affected

LNX2 (HGNC:20421): (ligand of numb-protein X 2) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in protein ubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

LNX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 13-27556336-G-A is Benign according to our data. Variant chr13-27556336-G-A is described in ClinVar as [Benign]. Clinvar id is 776786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.26 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1530/152166) while in subpopulation AFR AF= 0.0314 (1302/41514). AF 95% confidence interval is 0.0299. There are 27 homozygotes in gnomad4. There are 748 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LNX2	NM_153371.4 linkuse as main transcript	c.1446C>T	p.Thr482=	synonymous_variant	7/10	ENST00000316334.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LNX2	ENST00000316334.5 linkuse as main transcript	c.1446C>T	p.Thr482=	synonymous_variant	7/10	1	NM_153371.4	P1
LNX2	ENST00000649248.1 linkuse as main transcript	c.1446C>T	p.Thr482=	synonymous_variant	8/11			P1

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1530

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0315

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00747

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00340

AC:

853

AN:

250940

Hom.:

AF XY:

0.00264

AC XY:

358

AN XY:

135600

show subpopulations

Gnomad AFR exome

AF:

0.0330

Gnomad AMR exome

AF:

0.00457

Gnomad ASJ exome

AF:

0.000795

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00103

Gnomad OTH exome

AF:

0.00360

GnomAD4 exome

AF:

0.00171

AC:

2498

AN:

1461754

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

1165

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.0338

Gnomad4 AMR exome

AF:

0.00501

Gnomad4 ASJ exome

AF:

0.000804

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000359

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000682

Gnomad4 OTH exome

AF:

0.00421

GnomAD4 genome

AF:

0.0101

AC:

1530

AN:

152166

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

748

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0314

Gnomad4 AMR

AF:

0.00746

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00116

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00605

Hom.:

Bravo

AF:

0.0120

Asia WGS

AF:

0.00202

AC:

AN:

3476

EpiCase

AF:

0.00153

EpiControl

AF:

0.00184

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	Apr 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.3

DANN

Benign

0.55

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