rs915179

Positions:

• chr1-156108458-A-G
• chr1-156108458-A-T

Variant summary

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

The NM_001406983.1(LMNA):​c.-206-6255A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,896 control chromosomes in the GnomAD database, including 19,289 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 0.49 (19289 hom., cov: 31)
• Consequence: LMNA NM_001406983.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.706

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMNA	NM_001406983.1	c.-206-6255A>G		intron_variant			NP_001393912.1
LMNA	NM_001406991.1	c.-207+1635A>G		intron_variant			NP_001393920.1
LMNA	NM_001282625.2	c.-206-6255A>G		intron_variant			NP_001269554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMNA	ENST00000675667.1	c.-250+1635A>G		intron_variant				ENSP00000501803.1
LMNA	ENST00000675939.1	c.-206-6255A>G		intron_variant				ENSP00000502256.1
LMNA	ENST00000676385.2	c.-250+3541A>G		intron_variant				ENSP00000502091.1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74014 AN: 151778 Hom.: 19245 Cov.: 31

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.488 AC: 74108 AN: 151896 Hom.: 19289 Cov.: 31 AF XY: 0.488 AC XY: 36216 AN XY: 74242

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.791

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.463

Alfa AF: 0.431 Hom.: 7772

Bravo AF: 0.498

Asia WGS AF: 0.619 AC: 2148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs915179; hg19: chr1-156078249;