rs201524951

chr19-2456679-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_032737.4(LMNB2):c.255C>G(p.Thr85=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000755 in 1,543,186 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 30)
  • Exomes 𝑓: 0.00071 (4 hom.)
• Consequence: LMNB2 NM_032737.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.771

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 19-2456679-G-C is Benign according to our data. Variant chr19-2456679-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 542445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.771 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMNB2	NM_032737.4	c.255C>G	p.Thr85=	synonymous_variant	1/12	ENST00000325327.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMNB2	ENST00000325327.4	c.255C>G	p.Thr85=	synonymous_variant	1/12	1	NM_032737.4	P1

Frequencies

GnomAD3 genomes AF: 0.00115 AC: 174 AN: 151732 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00544

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00149

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00129 AC: 246 AN: 190622 Hom.: 1 AF XY: 0.00132 AC XY: 141 AN XY: 106832

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000142

Gnomad ASJ exome AF: 0.00452

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00429

Gnomad NFE exome AF: 0.00127

Gnomad OTH exome AF: 0.00226

GnomAD4 exome AF: 0.000712 AC: 991 AN: 1391346 Hom.: 4 Cov.: 31 AF XY: 0.000771 AC XY: 533 AN XY: 691584

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000130

Gnomad4 ASJ exome AF: 0.00414

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00433

Gnomad4 NFE exome AF: 0.000590

Gnomad4 OTH exome AF: 0.000602

GnomAD4 genome AF: 0.00115 AC: 174 AN: 151840 Hom.: 1 Cov.: 30 AF XY: 0.00139 AC XY: 103 AN XY: 74212

Gnomad4 AFR AF: 0.0000723

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00544

Gnomad4 NFE AF: 0.00149

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00179 Hom.: 0

Bravo AF: 0.000525

ClinVar

Significance: Benign/Likely 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	Jun 17, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	LMNB2: BP4, BP7 -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	14
Dann	Benign	0.89
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

Other links and lift over

dbSNP: rs201524951; hg19: chr19-2456677; COSMIC: COSV57591090; COSMIC: COSV57591090;