1-156137072-C-T

Variant names:

Variant summary

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

The NM_170707.4(LMNA):c.1489-41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0883 in 1,613,822 control chromosomes in the GnomAD database, including 11,376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 3906 hom., cov: 32)

Exomes 𝑓: 0.080 ( 7470 hom. )

Consequence

LMNA
NM_170707.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 0.386

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=-0.81).

BP6

Variant 1-156137072-C-T is Benign according to our data. Variant chr1-156137072-C-T is described in ClinVar as [Benign]. Clinvar id is 66834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-156137072-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMNA	NM_170707.4 link	c.1489-41C>T		intron_variant	Intron 8 of 11	ENST00000368300.9	NP_733821.1	P02545-1A0A384MQX1
LMNA	NM_005572.4 link	c.1489-41C>T		intron_variant	Intron 8 of 9	ENST00000677389.1	NP_005563.1	P02545-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMNA	ENST00000368300.9 link	c.1489-41C>T		intron_variant	Intron 8 of 11	1	NM_170707.4	ENSP00000357283.4		P02545-1
LMNA	ENST00000677389.1 link	c.1489-41C>T		intron_variant	Intron 8 of 9		NM_005572.4	ENSP00000503633.1		P02545-2

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25410

AN:

151958

Hom.:

3896

Cov.:

show subpopulations

Gnomad AFR

AF:

0.413

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0904

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.0228

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.0567

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.0703

Gnomad OTH

AF:

0.136

GnomAD3 exomes

AF:

0.0992

AC:

24904

AN:

251016

Hom.:

2317

AF XY:

0.0979

AC XY:

13281

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.428

Gnomad AMR exome

AF:

0.0634

Gnomad ASJ exome

AF:

0.132

Gnomad EAS exome

AF:

0.0192

Gnomad SAS exome

AF:

0.138

Gnomad FIN exome

AF:

0.0556

Gnomad NFE exome

AF:

0.0716

Gnomad OTH exome

AF:

0.0906

GnomAD4 exome

AF:

0.0801

AC:

117113

AN:

1461746

Hom.:

7470

Cov.:

AF XY:

0.0822

AC XY:

59756

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.430

Gnomad4 AMR exome

AF:

0.0661

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.0159

Gnomad4 SAS exome

AF:

0.140

Gnomad4 FIN exome

AF:

0.0543

Gnomad4 NFE exome

AF:

0.0664

Gnomad4 OTH exome

AF:

0.0990

GnomAD4 genome

AF:

0.167

AC:

25450

AN:

152076

Hom.:

3906

Cov.:

AF XY:

0.164

AC XY:

12218

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.413

Gnomad4 AMR

AF:

0.0903

Gnomad4 ASJ

AF:

0.132

Gnomad4 EAS

AF:

0.0226

Gnomad4 SAS

AF:

0.127

Gnomad4 FIN

AF:

0.0567

Gnomad4 NFE

AF:

0.0703

Gnomad4 OTH

AF:

0.135

Alfa

AF:

0.0874

Hom.:

1517

Bravo

AF:

0.179

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Epithelial Biology; Institute of Medical Biology, Singapore

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.1

DANN

Benign

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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

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