Variant rs375918278 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_032737.4(LMNB2):c.855+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00041 in 1,234,354 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00042 ( 9 hom. )

Consequence

LMNB2
NM_032737.4 splice_region, intron

Scores

Splicing: ADA: 0.0005497

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.499

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:

MIR7108 (HGNC:):

MIR7108 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 19-2434993-G-A is Benign according to our data. Variant chr19-2434993-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 542444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 9 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
LMNB2	NM_032737.4 linkuse as main transcript	c.855+8C>T	splice_region_variant, intron_variant		ENST00000325327.4	NP_116126.3	Q03252
MIR7108	NR_106958.1 linkuse as main transcript	n.8C>T	non_coding_transcript_exon_variant	1/1
MIR7108	unassigned_transcript_3192 use as main transcript	n.8C>T	non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMNB2	ENST00000325327.4 linkuse as main transcript	c.855+8C>T		splice_region_variant, intron_variant		1	NM_032737.4	ENSP00000327054.3		Q03252

Frequencies

GnomAD3 genomes

AF:

0.000362

AC:

AN:

143742

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000960

Gnomad ASJ

AF:

0.00419

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00233

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000122

Gnomad OTH

AF:

0.000978

GnomAD3 exomes

AF:

0.000553

AC:

128

AN:

231436

Hom.:

AF XY:

0.000665

AC XY:

AN XY:

127852

show subpopulations

Gnomad AFR exome

AF:

0.0000686

Gnomad AMR exome

AF:

0.000322

Gnomad ASJ exome

AF:

0.00341

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00227

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000116

Gnomad OTH exome

AF:

0.000347

GnomAD4 exome

AF:

0.000416

AC:

454

AN:

1090472

Hom.:

Cov.:

AF XY:

0.000540

AC XY:

295

AN XY:

546236

show subpopulations

Gnomad4 AFR exome

AF:

0.00118

Gnomad4 AMR exome

AF:

0.000546

Gnomad4 ASJ exome

AF:

0.00403

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00229

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000785

Gnomad4 OTH exome

AF:

0.00150

GnomAD4 genome

AF:

0.000361

AC:

AN:

143882

Hom.:

Cov.:

AF XY:

0.000385

AC XY:

AN XY:

70144

show subpopulations

Gnomad4 AFR

AF:

0.000124

Gnomad4 AMR

AF:

0.000958

Gnomad4 ASJ

AF:

0.00419

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00232

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000122

Gnomad4 OTH

AF:

0.000968

Alfa

AF:

0.000429

Hom.:

Bravo

AF:

0.000563

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely 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

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

LMNB2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 24, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.5

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00055

dbscSNV1_RF

Benign

0.022

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