19-2434925-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_032737.4(LMNB2):​c.856-12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000325 in 1,598,946 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000035 ( 2 hom. )

Consequence

LMNB2
NM_032737.4 intron

Scores

2
Splicing: ADA: 0.00001684
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.61
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 -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.03).
BP6
Variant 19-2434925-C-T is Benign according to our data. Variant chr19-2434925-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2202643.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 2 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LMNB2NM_032737.4 linkuse as main transcriptc.856-12G>A intron_variant ENST00000325327.4 NP_116126.3 Q03252
MIR7108NR_106958.1 linkuse as main transcriptn.76G>A non_coding_transcript_exon_variant 1/1
MIR7108unassigned_transcript_3191 use as main transcriptn.9G>A non_coding_transcript_exon_variant 1/1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LMNB2ENST00000325327.4 linkuse as main transcriptc.856-12G>A intron_variant 1 NM_032737.4 ENSP00000327054.3 Q03252
LMNB2ENST00000490554.5 linkuse as main transcriptn.35G>A non_coding_transcript_exon_variant 1/42
MIR7108ENST00000614319.1 linkuse as main transcriptn.76G>A non_coding_transcript_exon_variant 1/16
LMNB2ENST00000527409.1 linkuse as main transcriptn.492-12G>A intron_variant 5

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152150
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000721
AC:
16
AN:
221896
Hom.:
1
AF XY:
0.0000732
AC XY:
9
AN XY:
122876
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000471
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000102
Gnomad OTH exome
AF:
0.000178
GnomAD4 exome
AF:
0.0000353
AC:
51
AN:
1446680
Hom.:
2
Cov.:
34
AF XY:
0.0000417
AC XY:
30
AN XY:
719408
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000507
Gnomad4 SAS exome
AF:
0.000397
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000992
Gnomad4 OTH exome
AF:
0.0000334
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152266
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000151
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
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), LabcorpOct 19, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.22
DANN
Benign
0.76
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.6

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000017
dbscSNV1_RF
Benign
0.0
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: rs759357811; hg19: chr19-2434923; API