rs202012198

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The ENST00000325327.4(LMNB2):​c.1278C>T​(p.Ser426=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000256 in 1,603,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

LMNB2
ENST00000325327.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.147
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 19-2434030-G-A is Benign according to our data. Variant chr19-2434030-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 586126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.147 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LMNB2NM_032737.4 linkuse as main transcriptc.1278C>T p.Ser426= synonymous_variant 8/12 ENST00000325327.4 NP_116126.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LMNB2ENST00000325327.4 linkuse as main transcriptc.1278C>T p.Ser426= synonymous_variant 8/121 NM_032737.4 ENSP00000327054 P1
LMNB2ENST00000490554.5 linkuse as main transcriptn.469C>T non_coding_transcript_exon_variant 3/42

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152240
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000723
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000234
AC:
34
AN:
1451278
Hom.:
0
Cov.:
36
AF XY:
0.0000277
AC XY:
20
AN XY:
721658
show subpopulations
Gnomad4 AFR exome
AF:
0.0000902
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000351
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000244
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.0000459
AC:
7
AN:
152358
Hom.:
0
Cov.:
33
AF XY:
0.0000403
AC XY:
3
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.0000721
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000283
Hom.:
0
Bravo
AF:
0.0000302

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 23, 2023- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingAthena DiagnosticsNov 17, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
5.5
DANN
Benign
0.66

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs202012198; hg19: chr19-2434028; API