2-48755616-GGCTGCA-GGCTGCAGCTGCA

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_000233.4(LHCGR):c.50_55dupTGCAGC(p.Leu17_Gln18dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,531,600 control chromosomes in the GnomAD database, including 47,276 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3903 hom., cov: 25)

Exomes 𝑓: 0.25 ( 43373 hom. )

Consequence

LHCGR
NM_000233.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:7

Conservation

PhyloP100: 0.0830

Publications

2 publications found

Variant links:

Genes affected

LHCGR (HGNC:6585): (luteinizing hormone/choriogonadotropin receptor) This gene encodes the receptor for both luteinizing hormone and choriogonadotropin. This receptor belongs to the G-protein coupled receptor 1 family, and its activity is mediated by G proteins which activate adenylate cyclase. Mutations in this gene result in disorders of male secondary sexual character development, including familial male precocious puberty, also known as testotoxicosis, hypogonadotropic hypogonadism, Leydig cell adenoma with precocious puberty, and male pseudohermaphtoditism with Leydig cell hypoplasia. [provided by RefSeq, Jul 2008]

LHCGR links:

ENSG00000279956 (HGNC:):

ENSG00000279956 links:

STON1-GTF2A1L (HGNC:30651): (STON1-GTF2A1L readthrough) STON1-GTF2A1L mRNAs are infrequent but naturally occurring read-through products of the neighboring STON1 and GTF2A1L genes. These transcripts encode fusion proteins composed of the vast majority of each of the individual elements, stonin 1 and general transcription factor IIA, 1-like. Alternative splicing results in multiple transcript variants. The significance of these read-through variants and the function of the resulting protein products have not yet been determined. [provided by RefSeq, Oct 2010]

STON1-GTF2A1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_000233.4

BP6

Variant 2-48755616-G-GGCTGCA is Benign according to our data. Variant chr2-48755616-G-GGCTGCA is described in ClinVar as Benign. ClinVar VariationId is 336471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHCGR	NM_000233.4 link	c.50_55dupTGCAGC	p.Leu17_Gln18dup	conservative_inframe_insertion	Exon 1 of 11	ENST00000294954.12	NP_000224.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHCGR	ENST00000294954.12 link	c.50_55dupTGCAGC	p.Leu17_Gln18dup	conservative_inframe_insertion	Exon 1 of 11	1	NM_000233.4	ENSP00000294954.6
ENSG00000279956	ENST00000602369.3 link	n.50_55dupTGCAGC		non_coding_transcript_exon_variant	Exon 1 of 13	5		ENSP00000473498.1

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33267

AN:

151786

Hom.:

3909

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.358

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.0114

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.293

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.241

GnomAD2 exomes

AF:

0.190

AC:

25112

AN:

132330

AF XY:

0.189

show subpopulations

Gnomad AFR exome

AF:

0.176

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.0114

Gnomad FIN exome

AF:

0.181

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.229

GnomAD4 exome

AF:

0.246

AC:

339426

AN:

1379704

Hom.:

43373

Cov.:

AF XY:

0.242

AC XY:

164931

AN XY:

680642

show subpopulations

African (AFR)

AF:

0.179

AC:

5608

AN:

31380

American (AMR)

AF:

0.135

AC:

4794

AN:

35526

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

7308

AN:

24990

East Asian (EAS)

AF:

0.00841

AC:

300

AN:

35686

South Asian (SAS)

AF:

0.131

AC:

10313

AN:

78936

European-Finnish (FIN)

AF:

0.191

AC:

7102

AN:

37190

Middle Eastern (MID)

AF:

0.286

AC:

1157

AN:

4050

European-Non Finnish (NFE)

AF:

0.269

AC:

289229

AN:

1074474

Other (OTH)

AF:

0.237

AC:

13615

AN:

57472

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

12769

25537

38306

51074

63843

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9686

19372

29058

38744

48430

<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:

0.219

AC:

33261

AN:

151896

Hom.:

3903

Cov.:

AF XY:

0.210

AC XY:

15607

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.187

AC:

7743

AN:

41450

American (AMR)

AF:

0.185

AC:

2831

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

1041

AN:

3464

East Asian (EAS)

AF:

0.0114

AC:

AN:

5164

South Asian (SAS)

AF:

0.119

AC:

573

AN:

4828

European-Finnish (FIN)

AF:

0.188

AC:

1993

AN:

10596

Middle Eastern (MID)

AF:

0.288

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.267

AC:

18112

AN:

67808

Other (OTH)

AF:

0.238

AC:

502

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1289

2578

3867

5156

6445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

342

684

1026

1368

1710

<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:

0.173

Hom.:

446

Asia WGS

AF:

0.0840

AC:

295

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Aug 23, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 26, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 24, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Luteinizing hormone/choriogonadotropin receptor, lq variant

Pathogenic:1

Apr 01, 2003

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

Hypergonadotropic hypogonadism

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Leydig cell agenesis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Gonadotropin-independent familial sexual precocity

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.083

Mutation Taster

=87/13

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over