NM_005573.4:c.29G>C

Variant names:

• chr5-126777537-G-C
• NM_005573.4:c.29G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005573.4(LMNB1):​c.29G>C​(p.Arg10Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000793 in 1,261,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R10L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: LMNB1 NM_005573.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2462635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMNB1	NM_005573.4	c.29G>C	p.Arg10Pro	missense_variant	Exon 1 of 11	ENST00000261366.10	NP_005564.1
LMNB1	NM_001198557.2	c.-272+293G>C		intron_variant	Intron 1 of 10		NP_001185486.1
LMNB1	NR_134488.1	n.915G>C		non_coding_transcript_exon_variant	Exon 1 of 12
LMNB1	NR_177109.1	n.402G>C		non_coding_transcript_exon_variant	Exon 1 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMNB1	ENST00000261366.10	c.29G>C	p.Arg10Pro	missense_variant	Exon 1 of 11	1	NM_005573.4	ENSP00000261366.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.93e-7 AC: 1 AN: 1261466 Hom.: 0 Cov.: 30 AF XY: 0.00000162 AC XY: 1 AN XY: 617238

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: 9.87e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	23
DANN	Benign	0.96
DEOGEN2	Uncertain	0.58	D;T;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.75	T;T;T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.4	N;.;N
REVEL	Uncertain	0.46
Sift	Uncertain	0.0060	D;.;D
Sift4G	Benign	0.28	T;T;T
Polyphen		0.0020	B;.;.
Vest4		0.17
MutPred		0.29		Loss of MoRF binding (P = 0.0099);Loss of MoRF binding (P = 0.0099);Loss of MoRF binding (P = 0.0099);
MVP		0.91
MPC		0.60
ClinPred		0.24	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-126113229;