rs4807263

Variant names:

• chr19-2431274-T-G
• rs4807263
• NM_032737.4:c.1821+274A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-2431274-T-G
• chr19-2431274-T-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• microcephaly 27, primary, autosomal dominant

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• progressive myoclonic epilepsy type 9

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• microcephaly

  Inheritance: AD Classification: MODERATE Submitted by: Franklin by Genoox
• lipodystrophy, partial, acquired, susceptibility to

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• central nervous system malformation

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032737.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMNB2	NM_032737.4	MANE Select	c.1821+274A>C		intron	N/A	NP_116126.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMNB2	ENST00000325327.4	TSL:1 MANE Select	c.1821+274A>C		intron	N/A	ENSP00000327054.3	Q03252
	LMNB2	ENST00000917224.1		c.1962+274A>C		intron	N/A	ENSP00000587283.1
	LMNB2	ENST00000917223.1		c.1827+274A>C		intron	N/A	ENSP00000587282.1

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

African (AFR) AF: 0.236 AC: 9797 AN: 41480

American (AMR) AF: 0.257 AC: 3927 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1045 AN: 3470

East Asian (EAS) AF: 0.293 AC: 1514 AN: 5166

South Asian (SAS) AF: 0.493 AC: 2381 AN: 4826

European-Finnish (FIN) AF: 0.297 AC: 3141 AN: 10572

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22471 AN: 67946

Other (OTH) AF: 0.276 AC: 583 AN: 2114

Alfa AF: 0.304 Hom.: 9049

Bravo AF: 0.286

Asia WGS AF: 0.380 AC: 1321 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.22
DANN	Benign	0.51
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4807263; hg19: chr19-2431272; COSMIC: COSV53113764; COSMIC: COSV53113764;