chr1-201915824-T-C

Variant names:

• chr1-201915824-T-C
• rs2819348
• NM_012134.3:c.262-15073A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

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]

LMOD1 Gene-Disease associations (from GenCC):

• megacystis-microcolon-intestinal hypoperistalsis syndrome 3

  Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• megacystis-microcolon-intestinal hypoperistalsis syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LMOD1	NM_012134.3	c.262-15073A>G		intron_variant	Intron 1 of 2	ENST00000367288.5	NP_036266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMOD1	ENST00000367288.5	c.262-15073A>G		intron_variant	Intron 1 of 2	1	NM_012134.3	ENSP00000356257.4

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

African (AFR) AF: 0.320 AC: 13242 AN: 41424

American (AMR) AF: 0.286 AC: 4366 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 673 AN: 3466

East Asian (EAS) AF: 0.107 AC: 551 AN: 5168

South Asian (SAS) AF: 0.269 AC: 1294 AN: 4812

European-Finnish (FIN) AF: 0.318 AC: 3349 AN: 10540

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23301 AN: 67952

Other (OTH) AF: 0.273 AC: 577 AN: 2110

Alfa AF: 0.316 Hom.: 14078

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
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2819348; hg19: chr1-201884952;