rs11578696

chr1-156087177-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001406983.1(LMNA):c.-207+3993A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0828 in 151,872 control chromosomes in the GnomAD database, including 748 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.083 (748 hom., cov: 32)
• Consequence: LMNA NM_001406983.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMNA	NM_001282625.2	c.-318-3294A>G		intron_variant
LMNA	NM_001406983.1	c.-207+3993A>G		intron_variant
LMNA	NM_001406984.1	c.-207+3993A>G		intron_variant
LMNA	NM_001407002.1	c.-651+3993A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMNA	ENST00000368301.6	c.-318-3294A>G		intron_variant		2
LMNA	ENST00000470835.1	n.271-3822A>G		intron_variant, non_coding_transcript_variant		3
LMNA	ENST00000502751.5	n.328+3993A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0829 AC: 12581 AN: 151786 Hom.: 748 Cov.: 32

Gnomad AFR AF: 0.0230

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0191

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.0814

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

GnomAD4 genome AF: 0.0828 AC: 12580 AN: 151872 Hom.: 748 Cov.: 32 AF XY: 0.0811 AC XY: 6012 AN XY: 74176

Gnomad4 AFR AF: 0.0230

Gnomad4 AMR AF: 0.0730

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.0192

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.0809

Alfa AF: 0.107 Hom.: 577

Bravo AF: 0.0772

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.0
Dann	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11578696; hg19: chr1-156056968;