chr19-2434943-C-T

Position:

• chr19-2434943-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032737.4(LMNB2):​c.856-30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,585,874 control chromosomes in the GnomAD database, including 27,546 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3356 hom., cov: 33)
  • Exomes 𝑓: 0.18 (24190 hom.)
• Consequence: LMNB2 NM_032737.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.12

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]

LMNB2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 19-2434943-C-T is Benign according to our data. Variant chr19-2434943-C-T is described in ClinVar as [Benign]. Clinvar id is 1267290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMNB2	NM_032737.4	c.856-30G>A		intron_variant		ENST00000325327.4	NP_116126.3
MIR7108	NR_106958.1	n.58G>A		non_coding_transcript_exon_variant	1/1
MIR7108	unassigned_transcript_3191	n.-10G>A		upstream_gene_variant
MIR7108	unassigned_transcript_3192	n.*37G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMNB2	ENST00000325327.4	c.856-30G>A		intron_variant		1	NM_032737.4	ENSP00000327054.3
LMNB2	ENST00000490554.5	n.17G>A		non_coding_transcript_exon_variant	1/4	2
MIR7108	ENST00000614319.1	n.58G>A		non_coding_transcript_exon_variant	1/1	6
LMNB2	ENST00000527409.1	n.492-30G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30826 AN: 151972 Hom.: 3352 Cov.: 33

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.0295

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.180

GnomAD3 exomes AF: 0.184 AC: 37218 AN: 202300 Hom.: 3626 AF XY: 0.185 AC XY: 20843 AN XY: 112692

Gnomad AFR exome AF: 0.294

Gnomad AMR exome AF: 0.157

Gnomad ASJ exome AF: 0.176

Gnomad EAS exome AF: 0.0305

Gnomad SAS exome AF: 0.193

Gnomad FIN exome AF: 0.234

Gnomad NFE exome AF: 0.198

Gnomad OTH exome AF: 0.190

GnomAD4 exome AF: 0.180 AC: 258632 AN: 1433788 Hom.: 24190 Cov.: 37 AF XY: 0.181 AC XY: 129110 AN XY: 712126

Gnomad4 AFR exome AF: 0.276

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.0295

Gnomad4 SAS exome AF: 0.186

Gnomad4 FIN exome AF: 0.219

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.203 AC: 30850 AN: 152086 Hom.: 3356 Cov.: 33 AF XY: 0.203 AC XY: 15105 AN XY: 74346

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.0292

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.178

Alfa AF: 0.130 Hom.: 297

Bravo AF: 0.201

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.86
CADD	Benign	1.1
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6

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: rs62122269; hg19: chr19-2434941;