Variant 19-2430639-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.29

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
LMNB2	NM_032737.4 linkuse as main transcript	c.*272G>C		3_prime_UTR_variant	12/12	ENST00000325327.4	NP_116126.3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
LMNB2	ENST00000325327.4 linkuse as main transcript	c.*272G>C	3_prime_UTR_variant	12/12	1	NM_032737.4	ENSP00000327054	P1
LMNB2	ENST00000475819.1 linkuse as main transcript	n.48-331G>C	intron_variant, non_coding_transcript_variant		5
LMNB2	ENST00000532465.1 linkuse as main transcript	n.413+909G>C	intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.470

AC:

71369

AN:

152008

Hom.:

17325

Cov.:

show subpopulations

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.:

AF XY:

0.470

AC XY:

97125

AN XY:

206862

show subpopulations

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.:

AF XY:

0.474

AC XY:

35236

AN XY:

74356

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over