rs11882908

chr19-2432452-C-Gchr19-2432452-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_032737.4(LMNB2):c.1554G>C(p.Thr518=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00544 in 1,613,582 control chromosomes in the GnomAD database, including 441 homozygotes. 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. T518T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.029 (235 hom., cov: 31)
  • Exomes 𝑓: 0.0030 (206 hom.)
• Consequence: LMNB2 NM_032737.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.992

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 19-2432452-C-G is Benign according to our data. Variant chr19-2432452-C-G is described in ClinVar as [Benign]. Clinvar id is 475776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.992 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMNB2	NM_032737.4	c.1554G>C	p.Thr518=	synonymous_variant	9/12	ENST00000325327.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMNB2	ENST00000325327.4	c.1554G>C	p.Thr518=	synonymous_variant	9/12	1	NM_032737.4	P1
LMNB2	ENST00000532465.1	n.146G>C		non_coding_transcript_exon_variant	2/5	3

Frequencies

GnomAD3 genomes AF: 0.0289 AC: 4395 AN: 151844 Hom.: 232 Cov.: 31

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0234

GnomAD3 exomes AF: 0.00776 AC: 1949 AN: 251148 Hom.: 96 AF XY: 0.00564 AC XY: 766 AN XY: 135786

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.00547

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.00293

GnomAD4 exome AF: 0.00298 AC: 4350 AN: 1461620 Hom.: 206 Cov.: 33 AF XY: 0.00261 AC XY: 1899 AN XY: 727134

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.00590

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000845

Gnomad4 OTH exome AF: 0.00682

GnomAD4 genome AF: 0.0291 AC: 4423 AN: 151962 Hom.: 235 Cov.: 31 AF XY: 0.0281 AC XY: 2084 AN XY: 74290

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.00177 Hom.: 3

Bravo AF: 0.0333

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 29, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

Lipodystrophy, partial, acquired, susceptibility to;C4225289:Progressive myoclonic epilepsy type 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	0.12
Dann	Benign	0.73

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

Other links and lift over

dbSNP: rs11882908; hg19: chr19-2432450;