rs3764582

chr19-2456879-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0210

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 -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	UniProt
LMNB2	NM_032737.4	c.55G>A	p.Ala19Thr	missense_variant	1/12	ENST00000325327.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMNB2	ENST00000325327.4	c.55G>A	p.Ala19Thr	missense_variant	1/12	1	NM_032737.4	P1

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 2918 AN: 146428 Hom.: 43 Cov.: 30

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: 70 AN: 2374 Hom.: 0 AF XY: 0.0319 AC XY: 39 AN XY: 1222

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.: 30 AF XY: 0.0256 AC XY: 11408 AN XY: 446376

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.: 43 Cov.: 30 AF XY: 0.0198 AC XY: 1413 AN XY: 71326

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.: 0

Bravo AF: 0.0205

ExAC AF: 0.0156 AC: 32

Asia WGS AF: 0.0310 AC: 93 AN: 3038

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jul 11, 2017

- -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	16
Dann	Uncertain	0.98
DEOGEN2	Benign	0.25	T
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.0034	T
MutationTaster	Benign	1.0	D;N
PrimateAI	Pathogenic	0.88	D
Sift4G	Benign	0.37	T
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

Other links and lift over

dbSNP: rs3764582; hg19: chr19-2456877; COSMIC: COSV57588122; COSMIC: COSV57588122;