rs748688330

Variant names:

• chr19-2430919-C-G
• NM_032737.4:c.1855G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-2430919-C-G
• chr19-2430919-C-T

Variant summary

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

The NM_032737.4(LMNB2):​c.1855G>C​(p.Val619Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LMNB2 NM_032737.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.562

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]

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=0.089586675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMNB2	NM_032737.4	c.1855G>C	p.Val619Leu	missense_variant	Exon 12 of 12	ENST00000325327.4	NP_116126.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMNB2	ENST00000325327.4	c.1855G>C	p.Val619Leu	missense_variant	Exon 12 of 12	1	NM_032737.4	ENSP00000327054.3
LMNB2	ENST00000475819.1	n.48-611G>C		intron_variant	Intron 1 of 1	5
LMNB2	ENST00000532465.1	n.413+629G>C		intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1452424 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 723202

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: 9.06e-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	0.11
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.64	T
REVEL	Benign	0.060
Sift4G	Benign	0.15	T
Vest4		0.17
MVP		0.14
MPC		0.25
ClinPred		0.39	T
GERP RS		-0.38
Varity_R		0.022
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-2430917;