Genetic Variant LMOD1:p.Lys493del (chr1-201899533-CCTT-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 1P and 2B. PM4_SupportingBP6_Moderate

The NM_012134.3(LMOD1):c.1477_1479delAAG(p.Lys493del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000291 in 1,613,914 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

LMOD1
NM_012134.3 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.13

Variant links:

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 links:

ENSG00000223774 (HGNC:):

ENSG00000223774 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_012134.3. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 1-201899533-CCTT-C is Benign according to our data. Variant chr1-201899533-CCTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 709014.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMOD1	NM_012134.3 link	c.1477_1479delAAG	p.Lys493del	conservative_inframe_deletion	Exon 2 of 3	ENST00000367288.5	NP_036266.2	P29536-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LMOD1	ENST00000367288.5 link	c.1477_1479delAAG	p.Lys493del	conservative_inframe_deletion	Exon 2 of 3	1	NM_012134.3	ENSP00000356257.4	P29536-1
ENSG00000223774	ENST00000414927.5 link	n.246-191_246-189delTCT		intron_variant	Intron 2 of 2	3
ENSG00000223774	ENST00000458139.1 link	n.352-191_352-189delTCT		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000639

AC:

159

AN:

248706

AF XY:

0.000578

show subpopulations

Gnomad AFR exome

AF:

0.0000648

Gnomad AMR exome

AF:

0.00365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.000249

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000304

AC:

445

AN:

1461598

Hom.:

AF XY:

0.000290

AC XY:

211

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

AC:

AN:

33478

Gnomad4 AMR exome

AF:

0.00329

AC:

147

AN:

44718

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26134

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39696

Gnomad4 SAS exome

AF:

0.0000116

AC:

AN:

86228

Gnomad4 FIN exome

AF:

0.0000375

AC:

AN:

53392

Gnomad4 NFE exome

AF:

0.000242

AC:

269

AN:

1111818

Gnomad4 Remaining exome

AF:

0.000265

AC:

AN:

60366

Heterozygous variant carriers

122

152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000164

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0000962

AC:

0.0000962232

AN:

0.0000962232

Gnomad4 AMR

AF:

0.000849

AC:

0.00084934

AN:

0.00084934

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000118

AC:

0.000117585

AN:

0.000117585

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000400

Hom.:

Bravo

AF:

0.000382

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=70/30

polymorphism

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over