Variant 1-156129878-T-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_001406988.1(LMNA):c.29T>G(p.Leu10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 769,892 control chromosomes in the GnomAD database, including 9,118 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 4791 hom., cov: 32)

Exomes 𝑓: 0.090 ( 4327 hom. )

Consequence

LMNA
NM_001406988.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.34

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 (MetaRNN=0.0017819703).

BP6

Variant 1-156129878-T-G is Benign according to our data. Variant chr1-156129878-T-G is described in ClinVar as [Benign]. Clinvar id is 192190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-156129878-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMNA	NM_170707.4 link	c.357-739T>G		intron_variant		ENST00000368300.9	NP_733821.1	P02545-1A0A384MQX1
LMNA	NM_005572.4 link	c.357-739T>G		intron_variant		ENST00000677389.1	NP_005563.1	P02545-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMNA	ENST00000368300.9 link	c.357-739T>G		intron_variant		1	NM_170707.4	ENSP00000357283.4		P02545-1
LMNA	ENST00000677389.1 link	c.357-739T>G		intron_variant			NM_005572.4	ENSP00000503633.1		P02545-2

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27542

AN:

151952

Hom.:

4757

Cov.:

show subpopulations

Gnomad AFR

AF:

0.461

Gnomad AMI

AF:

0.0846

Gnomad AMR

AF:

0.0943

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.0229

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.0565

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.0711

Gnomad OTH

AF:

0.149

GnomAD3 exomes

AF:

0.100

AC:

22581

AN:

225092

Hom.:

2252

AF XY:

0.100

AC XY:

12364

AN XY:

123588

show subpopulations

Gnomad AFR exome

AF:

0.480

Gnomad AMR exome

AF:

0.0650

Gnomad ASJ exome

AF:

0.132

Gnomad EAS exome

AF:

0.0195

Gnomad SAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.0565

Gnomad NFE exome

AF:

0.0721

Gnomad OTH exome

AF:

0.0937

GnomAD4 exome

AF:

0.0904

AC:

55866

AN:

617822

Hom.:

4327

Cov.:

AF XY:

0.0928

AC XY:

31185

AN XY:

336006

show subpopulations

Gnomad4 AFR exome

AF:

0.466

Gnomad4 AMR exome

AF:

0.0685

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.0155

Gnomad4 SAS exome

AF:

0.142

Gnomad4 FIN exome

AF:

0.0545

Gnomad4 NFE exome

AF:

0.0724

Gnomad4 OTH exome

AF:

0.108

GnomAD4 genome

AF:

0.182

AC:

27624

AN:

152070

Hom.:

4791

Cov.:

AF XY:

0.179

AC XY:

13340

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.461

Gnomad4 AMR

AF:

0.0941

Gnomad4 ASJ

AF:

0.132

Gnomad4 EAS

AF:

0.0228

Gnomad4 SAS

AF:

0.128

Gnomad4 FIN

AF:

0.0565

Gnomad4 NFE

AF:

0.0711

Gnomad4 OTH

AF:

0.149

Alfa

AF:

0.121

Hom.:

1263

Bravo

AF:

0.196

TwinsUK

AF:

0.0599

AC:

222

ALSPAC

AF:

0.0646

AC:

249

ESP6500AA

AF:

0.450

AC:

788

ESP6500EA

AF:

0.0721

AC:

287

ExAC

AF:

0.101

AC:

11773

Asia WGS

AF:

0.108

AC:

375

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

research

Biesecker Lab/Clinical Genomics Section, National Institutes of Health

Jun 24, 2013

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hutchinson-Gilford syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

0.11

Eigen_PC

Benign

-0.0031

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.31

MetaRNN

Benign

0.0018

MetaSVM

Uncertain

0.27

PROVEAN

Benign

-0.25

REVEL

Uncertain

0.32

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Vest4

0.28

ClinPred

0.065

GERP RS

4.4

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