Variant chr5-126777531-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000261366.10(LMNB1):c.23C>A(p.Pro8Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000931 in 1,396,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000080 ( 0 hom. )

Consequence

LMNB1
ENST00000261366.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.68

Variant links:

Genes affected

LMNB1 (HGNC:6637): (lamin B1) This gene encodes one of the two B-type lamin proteins and is a component of the nuclear lamina. A duplication of this gene is associated with autosomal dominant adult-onset leukodystrophy (ADLD). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

LMNB1 links:

LMNB1 (HGNC:):

LMNB1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15357518).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMNB1	NM_005573.4 linkuse as main transcript	c.23C>A	p.Pro8Gln	missense_variant	1/11	ENST00000261366.10	NP_005564.1	P20700
LMNB1	NM_001198557.2 linkuse as main transcript	c.-272+287C>A		intron_variant			NP_001185486.1	B4DZT3
LMNB1	NR_134488.1 linkuse as main transcript	n.909C>A		non_coding_transcript_exon_variant	1/12
LMNB1	NR_177109.1 linkuse as main transcript	n.396C>A		non_coding_transcript_exon_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMNB1	ENST00000261366.10 linkuse as main transcript	c.23C>A	p.Pro8Gln	missense_variant	1/11	1	NM_005573.4	ENSP00000261366.5		P20700

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000803

AC:

AN:

1244636

Hom.:

Cov.:

AF XY:

0.0000115

AC XY:

AN XY:

607834

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000994

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.23C>A (p.P8Q) alteration is located in exon 1 (coding exon 1) of the LMNB1 gene. This alteration results from a C to A substitution at nucleotide position 23, causing the proline (P) at amino acid position 8 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.32

T;T;T

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.54

T;T;T

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.8

L;.;.

MutationTaster

Benign

0.93

N;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.64

N;.;N

REVEL

Benign

0.19

Sift

Benign

0.31

T;.;T

Sift4G

Benign

0.51

T;T;T

Polyphen

0.49

P;.;.

Vest4

0.22

MutPred

0.24

Gain of MoRF binding (P = 0.0215);Gain of MoRF binding (P = 0.0215);Gain of MoRF binding (P = 0.0215);

MVP

0.30

MPC

0.55

ClinPred

0.12

GERP RS

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.043

gMVP

0.33

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.

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