19-2431274-T-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.1821+274A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,058 control chromosomes in the GnomAD database, including 6,988 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (6988 hom., cov: 33)
• Consequence: LMNB2 NM_032737.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.35

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=-0.89).
• BP6: Variant 19-2431274-T-G is Benign according to our data. Variant chr19-2431274-T-G is described in ClinVar as [Benign]. Clinvar id is 1248663.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMNB2	NM_032737.4	c.1821+274A>C		intron_variant		ENST00000325327.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMNB2	ENST00000325327.4	c.1821+274A>C		intron_variant		1	NM_032737.4	P1
LMNB2	ENST00000475819.1	n.47+509A>C		intron_variant, non_coding_transcript_variant		5
LMNB2	ENST00000532465.1	n.413+274A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45329 AN: 151940 Hom.: 6992 Cov.: 33

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.279

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.298 AC: 45326 AN: 152058 Hom.: 6988 Cov.: 33 AF XY: 0.301 AC XY: 22337 AN XY: 74312

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.276

Alfa AF: 0.307 Hom.: 7035

Bravo AF: 0.286

Asia WGS AF: 0.380 AC: 1321 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	-0.89
Cadd	Benign	0.22
Dann	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4807263; hg19: chr19-2431272; COSMIC: COSV53113764; COSMIC: COSV53113764;