Variant chr1-156139185-G-C 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_170707.4(LMNA):c.*79G>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 0.0889 in 1,608,040 control chromosomes in the GnomAD database, including 11,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 4059 hom., cov: 31)

Exomes 𝑓: 0.080 ( 7584 hom. )

Consequence

LMNA
NM_170707.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -0.0620

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:

LMNA (HGNC:):

LMNA 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=-0.9).

BP6

Variant 1-156139185-G-C is Benign according to our data. Variant chr1-156139185-G-C is described in ClinVar as [Benign]. Clinvar id is 66756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-156139185-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMNA	NM_170707.4 linkuse as main transcript	c.*79G>C		3_prime_UTR_variant	12/12	ENST00000368300.9	NP_733821.1	P02545-1A0A384MQX1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMNA	ENST00000368300.9 linkuse as main transcript	c.*79G>C		3_prime_UTR_variant	12/12	1	NM_170707.4	ENSP00000357283.4		P02545-1

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25736

AN:

151688

Hom.:

4048

Cov.:

show subpopulations

Gnomad AFR

AF:

0.421

Gnomad AMI

AF:

0.0846

Gnomad AMR

AF:

0.0905

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.0227

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.0567

Gnomad MID

AF:

0.194

Gnomad NFE

AF:

0.0704

Gnomad OTH

AF:

0.135

GnomAD4 exome

AF:

0.0804

AC:

117154

AN:

1456234

Hom.:

7584

Cov.:

AF XY:

0.0825

AC XY:

59754

AN XY:

724244

show subpopulations

Gnomad4 AFR exome

AF:

0.439

Gnomad4 AMR exome

AF:

0.0666

Gnomad4 ASJ exome

AF:

0.131

Gnomad4 EAS exome

AF:

0.0159

Gnomad4 SAS exome

AF:

0.140

Gnomad4 FIN exome

AF:

0.0539

Gnomad4 NFE exome

AF:

0.0665

Gnomad4 OTH exome

AF:

0.0998

GnomAD4 genome

AF:

0.170

AC:

25776

AN:

151806

Hom.:

4059

Cov.:

AF XY:

0.167

AC XY:

12365

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.421

Gnomad4 AMR

AF:

0.0903

Gnomad4 ASJ

AF:

0.132

Gnomad4 EAS

AF:

0.0225

Gnomad4 SAS

AF:

0.127

Gnomad4 FIN

AF:

0.0567

Gnomad4 NFE

AF:

0.0704

Gnomad4 OTH

AF:

0.134

Alfa

AF:

0.0335

Hom.:

Bravo

AF:

0.182

Asia WGS

AF:

0.0960

AC:

335

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
not provided, no classification provided	literature only	Epithelial Biology; Institute of Medical Biology, Singapore	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.9

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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