Genetic Variant NM_005573.4:c.18C>A (chr5-126777526-C-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_005573.4(LMNB1):c.18C>A(p.Pro6Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P6P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LMNB1
NM_005573.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.66

Publications

0 publications found

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 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: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP7

Synonymous conserved (PhyloP=1.66 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005573.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LMNB1	NM_005573.4	MANE Select	c.18C>A	p.Pro6Pro	synonymous	Exon 1 of 11	NP_005564.1	P20700
LMNB1	NM_001198557.2		c.-272+282C>A		intron	N/A	NP_001185486.1
LMNB1	NR_134488.1		n.904C>A		non_coding_transcript_exon	Exon 1 of 12

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LMNB1	ENST00000261366.10	TSL:1 MANE Select	c.18C>A	p.Pro6Pro	synonymous	Exon 1 of 11	ENSP00000261366.5	P20700
LMNB1	ENST00000395354.1	TSL:1	c.18C>A	p.Pro6Pro	synonymous	Exon 1 of 6	ENSP00000378761.1	E9PBF6
LMNB1	ENST00000460265.5	TSL:1	n.18C>A		non_coding_transcript_exon	Exon 1 of 12	ENSP00000486528.1	A0A0D9SFE5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1236836

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

603086

African (AFR)

AF:

0.00

AC:

AN:

24664

American (AMR)

AF:

0.00

AC:

AN:

13786

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18432

East Asian (EAS)

AF:

0.00

AC:

AN:

27440

South Asian (SAS)

AF:

0.00

AC:

AN:

53644

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42100

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3680

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1002682

Other (OTH)

AF:

0.00

AC:

AN:

50408

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

1.7

PromoterAI

0.086

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over