rs201233721

Variant names:

• chr1-156136473-C-T
• rs201233721
• NM_170707.4:c.1380+37C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_170707.4(LMNA):​c.1380+37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00025 in 1,531,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: LMNA NM_170707.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0360

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-156136473-C-T is Benign according to our data. Variant chr1-156136473-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262794.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00145 (221/152290) while in subpopulation AFR AF = 0.00498 (207/41576). AF 95% confidence interval is 0.00442. There are 0 homozygotes in GnomAd4. There are 109 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMNA	NM_170707.4	c.1380+37C>T		intron_variant	Intron 7 of 11	ENST00000368300.9	NP_733821.1
LMNA	NM_005572.4	c.1380+37C>T		intron_variant	Intron 7 of 9	ENST00000677389.1	NP_005563.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMNA	ENST00000368300.9	c.1380+37C>T		intron_variant	Intron 7 of 11	1	NM_170707.4	ENSP00000357283.4
LMNA	ENST00000677389.1	c.1380+37C>T		intron_variant	Intron 7 of 9		NM_005572.4	ENSP00000503633.1

Frequencies

GnomAD3 genomes AF: 0.00145 AC: 220 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00497

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000383 AC: 59 AN: 153906 AF XY: 0.000344

Gnomad AFR exome AF: 0.00543

Gnomad AMR exome AF: 0.000402

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000167

Gnomad OTH exome AF: 0.000226

GnomAD4 exome AF: 0.000117 AC: 162 AN: 1379170 Hom.: 0 Cov.: 27 AF XY: 0.000103 AC XY: 70 AN XY: 681718

Gnomad4 AFR exome AF: 0.00404 AC: 126 AN: 31196

Gnomad4 AMR exome AF: 0.000336 AC: 12 AN: 35766

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25078

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 35808

Gnomad4 SAS exome AF: 0.0000126 AC: 1 AN: 79104

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 47312

Gnomad4 NFE exome AF: 0.00000376 AC: 4 AN: 1063566

Gnomad4 Remaining exome AF: 0.000314 AC: 18 AN: 57306

GnomAD4 genome AF: 0.00145 AC: 221 AN: 152290 Hom.: 0 Cov.: 32 AF XY: 0.00146 AC XY: 109 AN XY: 74466

Gnomad4 AFR AF: 0.00498 AC: 0.00497883 AN: 0.00497883

Gnomad4 AMR AF: 0.000785 AC: 0.000785135 AN: 0.000785135

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.00 AC: 0 AN: 0

Gnomad4 OTH AF: 0.000946 AC: 0.000946074 AN: 0.000946074

Alfa AF: 0.000812 Hom.: 1

Bravo AF: 0.00167

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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: rs201233721; hg19: chr1-156106264;