Genetic Variant LMNB1-DT:n.26G>T (chr5-126776461-C-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NR_134485.1(LMNB1-DT):n.26G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 152,112 control chromosomes in the GnomAD database, including 35,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.68 ( 35336 hom., cov: 33)

Exomes 𝑓: 0.75 ( 1 hom. )

Consequence

LMNB1-DT
NR_134485.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.51

Publications

4 publications found

Variant links:

Genes affected

LMNB1-DT (HGNC:53089): (LMNB1 divergent transcript)

LMNB1-DT links:

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 Gene-Disease associations (from GenCC):

microcephaly 26, primary, autosomal dominant
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
adult-onset autosomal dominant demyelinating leukodystrophy
Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
microcephaly
Inheritance: AD Classification: STRONG Submitted by: Franklin by Genoox
autosomal dominant primary microcephaly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LMNB1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 5-126776461-C-A is Benign according to our data. Variant chr5-126776461-C-A is described in ClinVar as Benign. ClinVar VariationId is 1179859.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_134485.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMNB1-DT	NR_134485.1		n.26G>T		non_coding_transcript_exon	Exon 1 of 4
	LMNB1	NR_134488.1		n.-162C>A		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
LMNB1-DT	ENST00000509185.2	TSL:5	n.26G>T	non_coding_transcript_exon	Exon 1 of 4
LMNB1-DT	ENST00000815038.1		n.86G>T	non_coding_transcript_exon	Exon 1 of 2
LMNB1-DT	ENST00000815039.1		n.63G>T	non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.677

AC:

102918

AN:

151990

Hom.:

35325

Cov.:

show subpopulations

Gnomad AFR

AF:

0.557

Gnomad AMI

AF:

0.714

Gnomad AMR

AF:

0.694

Gnomad ASJ

AF:

0.778

Gnomad EAS

AF:

0.660

Gnomad SAS

AF:

0.738

Gnomad FIN

AF:

0.800

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.718

Gnomad OTH

AF:

0.689

GnomAD4 exome

AF:

0.750

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.677

AC:

102978

AN:

152108

Hom.:

35336

Cov.:

AF XY:

0.683

AC XY:

50791

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.557

AC:

23101

AN:

41452

American (AMR)

AF:

0.694

AC:

10616

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.778

AC:

2700

AN:

3470

East Asian (EAS)

AF:

0.660

AC:

3416

AN:

5172

South Asian (SAS)

AF:

0.738

AC:

3559

AN:

4822

European-Finnish (FIN)

AF:

0.800

AC:

8481

AN:

10596

Middle Eastern (MID)

AF:

0.735

AC:

216

AN:

294

European-Non Finnish (NFE)

AF:

0.718

AC:

48790

AN:

67988

Other (OTH)

AF:

0.686

AC:

1452

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1690

3380

5070

6760

8450

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

816

1632

2448

3264

4080

<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:

0.702

Hom.:

86888

Bravo

AF:

0.663

Asia WGS

AF:

0.678

AC:

2360

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.0090

(source)

DANN

Benign

0.46

PhyloP100

-1.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over