rs3764582

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 9/15 in silico tools predict 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

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

microcephaly 27, primary, autosomal dominant
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
progressive myoclonic epilepsy type 9
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
microcephaly
Inheritance: AD Classification: MODERATE Submitted by: Franklin by Genoox
lipodystrophy, partial, acquired, susceptibility to
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
central nervous system malformation
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

LMNB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LMNB2	NM_032737.4 link	c.55G>A	p.Ala19Thr	missense_variant	Exon 1 of 12	ENST00000325327.4	NP_116126.3	Q03252

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMNB2	ENST00000325327.4 link	c.55G>A	p.Ala19Thr	missense_variant	Exon 1 of 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

GnomAD2 exomes

AF:

0.0295

AC:

AN:

2374

AF XY:

0.0319

show subpopulations

Gnomad AFR exome

AF:

0.00

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

African (AFR)

AF:

0.0116

AC:

210

AN:

18054

American (AMR)

AF:

0.0229

AC:

AN:

3806

Ashkenazi Jewish (ASJ)

AF:

0.0116

AC:

AN:

8046

East Asian (EAS)

AF:

0.106

AC:

1213

AN:

11422

South Asian (SAS)

AF:

0.0164

AC:

304

AN:

18532

European-Finnish (FIN)

AF:

0.0216

AC:

283

AN:

13078

Middle Eastern (MID)

AF:

0.0173

AC:

AN:

2134

European-Non Finnish (NFE)

AF:

0.0253

AC:

21081

AN:

834706

Other (OTH)

AF:

0.0282

AC:

949

AN:

33622

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1247

2494

3740

4987

6234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0199

AC:

2918

AN:

146534

Hom.:

Cov.:

AF XY:

0.0198

AC XY:

1413

AN XY:

71326

show subpopulations

African (AFR)

AF:

0.0113

AC:

462

AN:

40814

American (AMR)

AF:

0.0184

AC:

272

AN:

14822

Ashkenazi Jewish (ASJ)

AF:

0.00855

AC:

AN:

3390

East Asian (EAS)

AF:

0.0844

AC:

421

AN:

4988

South Asian (SAS)

AF:

0.0136

AC:

AN:

4778

European-Finnish (FIN)

AF:

0.0148

AC:

128

AN:

8658

Middle Eastern (MID)

AF:

0.0377

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0220

AC:

1448

AN:

65860

Other (OTH)

AF:

0.0320

AC:

AN:

2032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

130

260

391

521

651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

not specified

Benign:1

Jul 11, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.25

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.35

MetaRNN

Benign

0.0034

PhyloP100

-0.021

PrimateAI

Pathogenic

0.88

Sift4G

Benign

0.37

Vest4

0.15

MPC

1.5

GERP RS

-0.21

PromoterAI

-0.056

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

Varity_R

0.022

gMVP

0.11

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

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rs3764582

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over