rs10737170

chr1-156094089-C-Achr1-156094089-C-Gchr1-156094089-C-T

Variant summary

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

The NM_001406983.1(LMNA):c.-207+10905C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,134 control chromosomes in the GnomAD database, including 61,549 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 0.90 (61549 hom., cov: 31)
• Consequence: LMNA NM_001406983.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMNA	NM_001282625.2	c.-207+3507C>A		intron_variant
LMNA	NM_001406983.1	c.-207+10905C>A		intron_variant
LMNA	NM_001406984.1	c.-207+10905C>A		intron_variant
LMNA	NM_001407002.1	c.-651+10905C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMNA	ENST00000368301.6	c.-207+3507C>A		intron_variant		2
LMNA	ENST00000676385.2	c.-403+311C>A		intron_variant
LMNA	ENST00000502751.5	n.328+10905C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136679 AN: 152016 Hom.: 61487 Cov.: 31

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.957

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.894

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

GnomAD4 genome AF: 0.899 AC: 136797 AN: 152134 Hom.: 61549 Cov.: 31 AF XY: 0.899 AC XY: 66866 AN XY: 74362

Gnomad4 AFR AF: 0.880

Gnomad4 AMR AF: 0.924

Gnomad4 ASJ AF: 0.857

Gnomad4 EAS AF: 0.917

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 0.887

Gnomad4 NFE AF: 0.907

Gnomad4 OTH AF: 0.895

Alfa AF: 0.902 Hom.: 84156

Bravo AF: 0.901

Asia WGS AF: 0.912 AC: 3172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.13
Dann	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10737170; hg19: chr1-156063880;