rs375918278

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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:4

Conservation

PhyloP100: 0.499

Publications

0 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 links:

MIR7108 (HGNC:49998): (microRNA 7108) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR7108 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
LMNB2	NM_032737.4 link	c.855+8C>T	splice_region_variant, intron_variant	Intron 5 of 11	ENST00000325327.4	NP_116126.3	Q03252
MIR7108	NR_106958.1 link	n.8C>T	non_coding_transcript_exon_variant	Exon 1 of 1
MIR7108	unassigned_transcript_3191	n.8C>T	non_coding_transcript_exon_variant	Exon 1 of 1
MIR7108	unassigned_transcript_3190	n.-60C>T	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMNB2	ENST00000325327.4 link	c.855+8C>T		splice_region_variant, intron_variant	Intron 5 of 11	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

GnomAD2 exomes

AF:

0.000553

AC:

128

AN:

231436

AF XY:

0.000665

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 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

African (AFR)

AF:

0.00118

AC:

AN:

24632

American (AMR)

AF:

0.000546

AC:

AN:

38440

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

AN:

16642

East Asian (EAS)

AF:

0.00

AC:

AN:

18184

South Asian (SAS)

AF:

0.00229

AC:

186

AN:

81052

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26294

Middle Eastern (MID)

AF:

0.00577

AC:

AN:

4158

European-Non Finnish (NFE)

AF:

0.0000785

AC:

AN:

840294

Other (OTH)

AF:

0.00150

AC:

AN:

40776

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

116

145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000361

AC:

AN:

143882

Hom.:

Cov.:

AF XY:

0.000385

AC XY:

AN XY:

70144

show subpopulations

African (AFR)

AF:

0.000124

AC:

AN:

40192

American (AMR)

AF:

0.000958

AC:

AN:

14618

Ashkenazi Jewish (ASJ)

AF:

0.00419

AC:

AN:

3338

East Asian (EAS)

AF:

0.00

AC:

AN:

4118

South Asian (SAS)

AF:

0.00232

AC:

AN:

3884

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9134

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.000122

AC:

AN:

65388

Other (OTH)

AF:

0.000968

AC:

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 13, 2024

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

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

LMNB2-related disorder

Benign:1

Oct 24, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

DANN

Benign

0.89

PhyloP100

0.50

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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