Variant 19-2456879-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032737.4(LMNB2):c.55G>A(p.Ala19Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0249 in 1,089,934 control chromosomes in the GnomAD database, including 354 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 43 hom., cov: 30)

Exomes 𝑓: 0.026 ( 311 hom. )

Consequence

LMNB2
NM_032737.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0210

Variant links:

Genes affected

LMNB2 (HGNC:6638): (lamin B2) This gene encodes a B type nuclear lamin. The nuclear lamina consists of a two-dimensional matrix of proteins located next to the inner nuclear membrane. The lamin family of proteins make up the matrix and are highly conserved in evolution. During mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are thought to be involved in nuclear stability, chromatin structure and gene expression. Vertebrate lamins consist of two types, A and B. Mutations in this gene are associated with acquired partial lipodystrophy. [provided by RefSeq, May 2012]

LMNB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034243166).

BP6

Variant 19-2456879-C-T is Benign according to our data. Variant chr19-2456879-C-T is described in ClinVar as [Benign]. Clinvar id is 447703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMNB2	NM_032737.4 linkuse as main transcript	c.55G>A	p.Ala19Thr	missense_variant	1/12	ENST00000325327.4	NP_116126.3	Q03252

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMNB2	ENST00000325327.4 linkuse as main transcript	c.55G>A	p.Ala19Thr	missense_variant	1/12	1	NM_032737.4	ENSP00000327054.3		Q03252

Frequencies

GnomAD3 genomes

AF:

0.0199

AC:

2918

AN:

146428

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0114

Gnomad AMI

AF:

0.0189

Gnomad AMR

AF:

0.0184

Gnomad ASJ

AF:

0.00855

Gnomad EAS

AF:

0.0839

Gnomad SAS

AF:

0.0136

Gnomad FIN

AF:

0.0148

Gnomad MID

AF:

0.0350

Gnomad NFE

AF:

0.0220

Gnomad OTH

AF:

0.0324

GnomAD3 exomes

AF:

0.0295

AC:

AN:

2374

Hom.:

AF XY:

0.0319

AC XY:

AN XY:

1222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad SAS exome

AF:

0.500

Gnomad FIN exome

AF:

0.0282

Gnomad NFE exome

AF:

0.0305

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0257

AC:

24257

AN:

943400

Hom.:

311

Cov.:

AF XY:

0.0256

AC XY:

11408

AN XY:

446376

show subpopulations

Gnomad4 AFR exome

AF:

0.0116

Gnomad4 AMR exome

AF:

0.0229

Gnomad4 ASJ exome

AF:

0.0116

Gnomad4 EAS exome

AF:

0.106

Gnomad4 SAS exome

AF:

0.0164

Gnomad4 FIN exome

AF:

0.0216

Gnomad4 NFE exome

AF:

0.0253

Gnomad4 OTH exome

AF:

0.0282

GnomAD4 genome

AF:

0.0199

AC:

2918

AN:

146534

Hom.:

Cov.:

AF XY:

0.0198

AC XY:

1413

AN XY:

71326

show subpopulations

Gnomad4 AFR

AF:

0.0113

Gnomad4 AMR

AF:

0.0184

Gnomad4 ASJ

AF:

0.00855

Gnomad4 EAS

AF:

0.0844

Gnomad4 SAS

AF:

0.0136

Gnomad4 FIN

AF:

0.0148

Gnomad4 NFE

AF:

0.0220

Gnomad4 OTH

AF:

0.0320

Alfa

AF:

0.0177

Hom.:

Bravo

AF:

0.0205

ExAC

AF:

0.0156

AC:

Asia WGS

AF:

0.0310

AC:

AN:

3038

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Lipodystrophy, partial, acquired, susceptibility to;C4225289:Progressive myoclonic epilepsy type 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jul 11, 2017

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.25

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.35

MetaRNN

Benign

0.0034

PrimateAI

Pathogenic

0.88

Sift4G

Benign

0.37

Vest4

0.15

MPC

1.5

GERP RS

-0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

Varity_R

0.022

gMVP

0.11

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