rs2819348

chr1-201915824-T-Cchr1-201915824-T-G

Variant summary

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

The NM_012134.3(LMOD1):c.262-15073A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,944 control chromosomes in the GnomAD database, including 7,704 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 0.31 (7704 hom., cov: 31)
• Consequence: LMOD1 NM_012134.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.888

Genes affected

LMOD1 (HGNC:6647): (leiomodin 1) The leiomodin 1 protein has a putative membrane-spanning region and 2 types of tandemly repeated blocks. The transcript is expressed in all tissues tested, with the highest levels in thyroid, eye muscle, skeletal muscle, and ovary. Increased expression of leiomodin 1 may be linked to Graves' disease and thyroid-associated ophthalmopathy. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMOD1	NM_012134.3	c.262-15073A>G		intron_variant		ENST00000367288.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMOD1	ENST00000367288.5	c.262-15073A>G		intron_variant		1	NM_012134.3	P1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47710 AN: 151828 Hom.: 7694 Cov.: 31

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.314 AC: 47741 AN: 151944 Hom.: 7704 Cov.: 31 AF XY: 0.310 AC XY: 23015 AN XY: 74232

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.273

Alfa AF: 0.312 Hom.: 6824

Bravo AF: 0.311

Asia WGS AF: 0.170 AC: 589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.0
Dann	Benign	0.65

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: rs2819348; hg19: chr1-201884952;