rs528636

Positions:

• chr1-156128829-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_170707.4(LMNA):​c.357-1788A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,256 control chromosomes in the GnomAD database, including 7,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.21 (7063 hom., cov: 32)
• Consequence: LMNA NM_170707.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-156128829-A-G is Benign according to our data. Variant chr1-156128829-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMNA	NM_170707.4	c.357-1788A>G		intron_variant		ENST00000368300.9	NP_733821.1
LMNA	NM_005572.4	c.357-1788A>G		intron_variant		ENST00000677389.1	NP_005563.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMNA	ENST00000368300.9	c.357-1788A>G		intron_variant		1	NM_170707.4	ENSP00000357283.4
LMNA	ENST00000677389.1	c.357-1788A>G		intron_variant			NM_005572.4	ENSP00000503633.1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32029 AN: 152138 Hom.: 7020 Cov.: 32

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0229

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0565

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.0712

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.211 AC: 32122 AN: 152256 Hom.: 7063 Cov.: 32 AF XY: 0.207 AC XY: 15421 AN XY: 74460

Gnomad4 AFR AF: 0.564

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.0228

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.0565

Gnomad4 NFE AF: 0.0712

Gnomad4 OTH AF: 0.168

Alfa AF: 0.153 Hom.: 527

Bravo AF: 0.228

Asia WGS AF: 0.111 AC: 388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.71
DANN	Benign	0.54

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

Other links and lift over

dbSNP: rs528636; hg19: chr1-156098620;