chr19-2431257-G-A

Position:

• chr19-2431257-G-A

Variant summary

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

The ENST00000325327.4(LMNB2):​c.1821+291C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 152,242 control chromosomes in the GnomAD database, including 450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.063 (450 hom., cov: 33)
• Consequence: LMNB2 ENST00000325327.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.26

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=-0.88).
• BP6: Variant 19-2431257-G-A is Benign according to our data. Variant chr19-2431257-G-A is described in ClinVar as [Benign]. Clinvar id is 1235386.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMNB2	NM_032737.4	c.1821+291C>T		intron_variant		ENST00000325327.4	NP_116126.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMNB2	ENST00000325327.4	c.1821+291C>T		intron_variant		1	NM_032737.4	ENSP00000327054	P1
LMNB2	ENST00000475819.1	n.47+526C>T		intron_variant, non_coding_transcript_variant		5
LMNB2	ENST00000532465.1	n.413+291C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0631 AC: 9596 AN: 152124 Hom.: 450 Cov.: 33

Gnomad AFR AF: 0.0649

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0703

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0372

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0478

Gnomad OTH AF: 0.0522

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

GnomAD4 genome AF: 0.0630 AC: 9596 AN: 152242 Hom.: 450 Cov.: 33 AF XY: 0.0655 AC XY: 4876 AN XY: 74436

Gnomad4 AFR AF: 0.0648

Gnomad4 AMR AF: 0.0701

Gnomad4 ASJ AF: 0.0415

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.0372

Gnomad4 NFE AF: 0.0478

Gnomad4 OTH AF: 0.0554

Alfa AF: 0.0530 Hom.: 35

Bravo AF: 0.0638

Asia WGS AF: 0.161 AC: 560 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	-0.88
CADD	Benign	1.1
DANN	Benign	0.61

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: rs57770804; hg19: chr19-2431255;