rs501791

chr1-156120082-C-T

Variant summary

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

The NM_170707.4(LMNA):c.356+4808C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,152 control chromosomes in the GnomAD database, including 3,714 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 (3714 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMNA	NM_005572.4	c.356+4808C>T		intron_variant		ENST00000677389.1
LMNA	NM_170707.4	c.356+4808C>T		intron_variant		ENST00000368300.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMNA	ENST00000368300.9	c.356+4808C>T		intron_variant		1	NM_170707.4	P1
LMNA	ENST00000677389.1	c.356+4808C>T		intron_variant			NM_005572.4

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22684 AN: 152034 Hom.: 3686 Cov.: 31

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0784

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0532

Gnomad FIN AF: 0.0307

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0490

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.150 AC: 22762 AN: 152152 Hom.: 3714 Cov.: 31 AF XY: 0.146 AC XY: 10866 AN XY: 74384

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.0782

Gnomad4 ASJ AF: 0.0971

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0534

Gnomad4 FIN AF: 0.0307

Gnomad4 NFE AF: 0.0490

Gnomad4 OTH AF: 0.122

Alfa AF: 0.145 Hom.: 502

Bravo AF: 0.164

Asia WGS AF: 0.0550 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	14
Dann	Benign	0.73

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: rs501791; hg19: chr1-156089873; COSMIC: COSV61542510; COSMIC: COSV61542510;