rs2485662

Positions:

• chr1-156113677-T-C

Variant summary

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

The NM_001406983.1(LMNA):​c.-206-1036T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 151,928 control chromosomes in the GnomAD database, including 34,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.66 (34257 hom., cov: 30)
• Consequence: LMNA NM_001406983.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272

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=-0.85).
• BP6: Variant 1-156113677-T-C is Benign according to our data. Variant chr1-156113677-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMNA	NM_001406983.1	c.-206-1036T>C		intron_variant			NP_001393912.1
LMNA	NM_001406991.1	c.-206-1036T>C		intron_variant			NP_001393920.1
LMNA	NM_001282625.2	c.-206-1036T>C		intron_variant			NP_001269554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMNA	ENST00000675667.1	c.-249-993T>C		intron_variant				ENSP00000501803.1
LMNA	ENST00000675939.1	c.-206-1036T>C		intron_variant				ENSP00000502256.1
LMNA	ENST00000683032.1	c.-206-1036T>C		intron_variant				ENSP00000506771.1

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99797 AN: 151812 Hom.: 34240 Cov.: 30

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.678

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

GnomAD4 genome AF: 0.657 AC: 99853 AN: 151928 Hom.: 34257 Cov.: 30 AF XY: 0.660 AC XY: 48979 AN XY: 74252

Gnomad4 AFR AF: 0.440

Gnomad4 AMR AF: 0.773

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.797

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.725

Gnomad4 OTH AF: 0.680

Alfa AF: 0.712 Hom.: 57557

Bravo AF: 0.654

Asia WGS AF: 0.826 AC: 2873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.4
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: rs2485662; hg19: chr1-156083468;