1-156085394-T-C

Position:

• chr1-156085394-T-C

Variant summary

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

The NM_001406983.1(LMNA):​c.-207+2210T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,112 control chromosomes in the GnomAD database, including 7,459 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 0.27 (7459 hom., cov: 32)
• Consequence: LMNA NM_001406983.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMNA	NM_001406983.1	c.-207+2210T>C		intron_variant			NP_001393912.1
LMNA	NM_001282625.2	c.-319+2210T>C		intron_variant			NP_001269554.1
LMNA	NM_001406984.1	c.-207+2210T>C		intron_variant			NP_001393913.1
LMNA	NM_001407002.1	c.-651+2210T>C		intron_variant			NP_001393931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMNA	ENST00000368301.6	c.-319+2210T>C		intron_variant		2		ENSP00000357284.2
LMNA	ENST00000470835.1	n.270+2210T>C		intron_variant		3
LMNA	ENST00000502751.5	n.328+2210T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40796 AN: 151994 Hom.: 7429 Cov.: 32

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.269 AC: 40881 AN: 152112 Hom.: 7459 Cov.: 32 AF XY: 0.269 AC XY: 19973 AN XY: 74368

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.244

Alfa AF: 0.230 Hom.: 1054

Bravo AF: 0.289

Asia WGS AF: 0.480 AC: 1665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12063564; hg19: chr1-156055185;