rs534807

Positions:

Variant summary

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

The NM_170707.4(LMNA):c.1157+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0893 in 1,613,538 control chromosomes in the GnomAD database, including 12,322 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 4497 hom., cov: 32)

Exomes 𝑓: 0.080 ( 7825 hom. )

Consequence

LMNA
NM_170707.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:15O:1

Conservation

PhyloP100: 0.575

Variant links:

Genes affected

LMNA (HGNC:6636): (lamin A/C) The protein encoded by this gene is part of the nuclear lamina, 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. Alternative splicing results in multiple transcript variants. Mutations in this gene lead to several diseases: Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease, and Hutchinson-Gilford progeria syndrome. [provided by RefSeq, May 2022]

LMNA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-156136137-G-A is Benign according to our data. Variant chr1-156136137-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 36474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-156136137-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMNA	NM_005572.4 linkuse as main transcript	c.1157+16G>A		intron_variant		ENST00000677389.1	NP_005563.1
LMNA	NM_170707.4 linkuse as main transcript	c.1157+16G>A		intron_variant		ENST00000368300.9	NP_733821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMNA	ENST00000368300.9 linkuse as main transcript	c.1157+16G>A		intron_variant		1	NM_170707.4	ENSP00000357283	P1	P02545-1
LMNA	ENST00000677389.1 linkuse as main transcript	c.1157+16G>A		intron_variant			NM_005572.4	ENSP00000503633		P02545-2

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26713

AN:

152062

Hom.:

4477

Cov.:

show subpopulations

Gnomad AFR

AF:

0.443

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0932

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.0225

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.0558

Gnomad MID

AF:

0.188

Gnomad NFE

AF:

0.0701

Gnomad OTH

AF:

0.141

GnomAD3 exomes

AF:

0.100

AC:

25124

AN:

250254

Hom.:

2494

AF XY:

0.0979

AC XY:

13260

AN XY:

135378

show subpopulations

Gnomad AFR exome

AF:

0.459

Gnomad AMR exome

AF:

0.0650

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.0191

Gnomad SAS exome

AF:

0.132

Gnomad FIN exome

AF:

0.0551

Gnomad NFE exome

AF:

0.0713

Gnomad OTH exome

AF:

0.0890

GnomAD4 exome

AF:

0.0803

AC:

117325

AN:

1461358

Hom.:

7825

Cov.:

AF XY:

0.0820

AC XY:

59603

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.460

Gnomad4 AMR exome

AF:

0.0672

Gnomad4 ASJ exome

AF:

0.129

Gnomad4 EAS exome

AF:

0.0158

Gnomad4 SAS exome

AF:

0.135

Gnomad4 FIN exome

AF:

0.0535

Gnomad4 NFE exome

AF:

0.0661

Gnomad4 OTH exome

AF:

0.0999

GnomAD4 genome

AF:

0.176

AC:

26776

AN:

152180

Hom.:

4497

Cov.:

AF XY:

0.173

AC XY:

12907

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.444

Gnomad4 AMR

AF:

0.0931

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.0224

Gnomad4 SAS

AF:

0.123

Gnomad4 FIN

AF:

0.0558

Gnomad4 NFE

AF:

0.0701

Gnomad4 OTH

AF:

0.140

Alfa

AF:

0.0715

Hom.:

160

Bravo

AF:

0.189

Asia WGS

AF:

0.101

AC:

351

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:15Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 19, 2013	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 15, 2008	- -

not provided

Benign:3Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jan 27, 2021	- -
not provided, no classification provided	literature only	Epithelial Biology; Institute of Medical Biology, Singapore	-	- -

Primary dilated cardiomyopathy

Benign:2

Benign, criteria provided, single submitter	clinical testing	Cohesion Phenomics	Sep 27, 2022	- -
Benign, no assertion criteria provided	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Aug 18, 2011	- -

Charcot-Marie-Tooth disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

Charcot-Marie-Tooth disease type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.2

DANN

Benign

0.39

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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