rs582690

Positions:

• chr1-156118465-C-G
• chr1-156118465-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_170707.4(LMNA):​c.356+3191C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,002 control chromosomes in the GnomAD database, including 3,708 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 0.15 (3708 hom., cov: 31)
• Consequence: LMNA NM_170707.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMNA	NM_005572.4	c.356+3191C>G		intron_variant		ENST00000677389.1
LMNA	NM_170707.4	c.356+3191C>G		intron_variant		ENST00000368300.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMNA	ENST00000368300.9	c.356+3191C>G		intron_variant		1	NM_170707.4	P1
LMNA	ENST00000677389.1	c.356+3191C>G		intron_variant			NM_005572.4

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22547 AN: 151884 Hom.: 3677 Cov.: 31

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.0789

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0533

Gnomad FIN AF: 0.0304

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0489

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.149 AC: 22626 AN: 152002 Hom.: 3708 Cov.: 31 AF XY: 0.145 AC XY: 10794 AN XY: 74336

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.0787

Gnomad4 ASJ AF: 0.0971

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.0533

Gnomad4 FIN AF: 0.0304

Gnomad4 NFE AF: 0.0489

Gnomad4 OTH AF: 0.121

Alfa AF: 0.0213 Hom.: 18

Bravo AF: 0.162

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Benign	0.80

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: rs582690; hg19: chr1-156088256;