19-2430639-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032737.4(LMNB2):c.*272G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 540,632 control chromosomes in the GnomAD database, including 60,296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.47 (17344 hom., cov: 33)
  • Exomes 𝑓: 0.46 (42952 hom.)
• Consequence: LMNB2 NM_032737.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.29

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 19-2430639-C-G is Benign according to our data. Variant chr19-2430639-C-G is described in ClinVar as [Benign]. Clinvar id is 1245133.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMNB2	NM_032737.4	c.*272G>C		3_prime_UTR_variant	12/12	ENST00000325327.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMNB2	ENST00000325327.4	c.*272G>C		3_prime_UTR_variant	12/12	1	NM_032737.4	P1
LMNB2	ENST00000475819.1	n.48-331G>C		intron_variant, non_coding_transcript_variant		5
LMNB2	ENST00000532465.1	n.413+909G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71369 AN: 152008 Hom.: 17325 Cov.: 33

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.425

GnomAD4 exome AF: 0.460 AC: 178592 AN: 388506 Hom.: 42952 Cov.: 0 AF XY: 0.470 AC XY: 97125 AN XY: 206862

Gnomad4 AFR exome AF: 0.558

Gnomad4 AMR exome AF: 0.332

Gnomad4 ASJ exome AF: 0.329

Gnomad4 EAS exome AF: 0.673

Gnomad4 SAS exome AF: 0.603

Gnomad4 FIN exome AF: 0.421

Gnomad4 NFE exome AF: 0.427

Gnomad4 OTH exome AF: 0.443

GnomAD4 genome AF: 0.470 AC: 71440 AN: 152126 Hom.: 17344 Cov.: 33 AF XY: 0.474 AC XY: 35236 AN XY: 74356

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.424

Alfa AF: 0.299 Hom.: 710

Bravo AF: 0.462

Asia WGS AF: 0.589 AC: 2046 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.066
Dann	Benign	0.65

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

Other links and lift over

dbSNP: rs1049910; hg19: chr19-2430637; COSMIC: COSV53115542; COSMIC: COSV53115542;