Variant rs267607650 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032737.4(LMNB2):c.265-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000382 in 1,608,482 control chromosomes in the GnomAD database, including 2 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 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00041 ( 2 hom. )

Consequence

LMNB2
NM_032737.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00006020

Clinical Significance

Likely benign criteria provided, single submitter B:1O:2

Conservation

PhyloP100: 3.15

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:

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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=-0.81).

BP6

Variant 19-2444546-G-A is Benign according to our data. Variant chr19-2444546-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 66746.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
LMNB2	NM_032737.4 linkuse as main transcript	c.265-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000325327.4	NP_116126.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMNB2	ENST00000325327.4 linkuse as main transcript	c.265-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_032737.4	ENSP00000327054	P1

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000105

AC:

AN:

246874

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

134090

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000194

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000409

AC:

595

AN:

1456228

Hom.:

Cov.:

AF XY:

0.000385

AC XY:

279

AN XY:

724608

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000523

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000131

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000186

Hom.:

Bravo

AF:

0.000144

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1Other:2

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

not provided

Other:1

not provided, no classification provided

literature only

Epithelial Biology; Institute of Medical Biology, Singapore

- -

Acquired partial lipodystrophy

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Aug 01, 2006

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.5

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000060

dbscSNV1_RF

Benign

0.018

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