rs2387588

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000894.3(LHB):c.183+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 1,375,700 control chromosomes in the GnomAD database, including 273,177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 29647 hom., cov: 28)

Exomes 𝑓: 0.59 ( 243530 hom. )

Consequence

LHB
NM_000894.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.12

Publications

7 publications found

Variant links:

Genes affected

LHB (HGNC:6584): (luteinizing hormone subunit beta) This gene is a member of the glycoprotein hormone beta chain family and encodes the beta subunit of luteinizing hormone (LH). Glycoprotein hormones are heterodimers consisting of a common alpha subunit and an unique beta subunit which confers biological specificity. LH is expressed in the pituitary gland and promotes spermatogenesis and ovulation by stimulating the testes and ovaries to synthesize steroids. The genes for the beta chains of chorionic gonadotropin and for luteinizing hormone are contiguous on chromosome 19q13.3. Mutations in this gene are associated with hypogonadism which is characterized by infertility and pseudohermaphroditism. [provided by RefSeq, Jul 2008]

LHB Gene-Disease associations (from GenCC):

hypogonadotropic hypogonadism 23 with or without anosmia
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

LHB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 19-49016536-A-G is Benign according to our data. Variant chr19-49016536-A-G is described in ClinVar as Benign. ClinVar VariationId is 518301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHB	NM_000894.3 link	c.183+11T>C		intron_variant	Intron 2 of 2	ENST00000649238.3	NP_000885.1	P01229A0A0F7RQE6
LHB	XM_047438832.1 link	c.231+11T>C		intron_variant	Intron 1 of 1		XP_047294788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHB	ENST00000649238.3 link	c.183+11T>C		intron_variant	Intron 2 of 2		NM_000894.3	ENSP00000497294.2		P01229
LHB	ENST00000649284.1 link	n.274+11T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.623

AC:

93259

AN:

149646

Hom.:

29618

Cov.:

show subpopulations

Gnomad AFR

AF:

0.718

Gnomad AMI

AF:

0.649

Gnomad AMR

AF:

0.666

Gnomad ASJ

AF:

0.559

Gnomad EAS

AF:

0.324

Gnomad SAS

AF:

0.541

Gnomad FIN

AF:

0.616

Gnomad MID

AF:

0.669

Gnomad NFE

AF:

0.590

Gnomad OTH

AF:

0.590

GnomAD2 exomes

AF:

0.581

AC:

129397

AN:

222778

AF XY:

0.574

show subpopulations

Gnomad AFR exome

AF:

0.723

Gnomad AMR exome

AF:

0.708

Gnomad ASJ exome

AF:

0.566

Gnomad EAS exome

AF:

0.305

Gnomad FIN exome

AF:

0.570

Gnomad NFE exome

AF:

0.578

Gnomad OTH exome

AF:

0.579

GnomAD4 exome

AF:

0.589

AC:

722550

AN:

1225936

Hom.:

243530

Cov.:

AF XY:

0.587

AC XY:

358163

AN XY:

610476

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.755

AC:

22866

AN:

30286

American (AMR)

AF:

0.718

AC:

27142

AN:

37780

Ashkenazi Jewish (ASJ)

AF:

0.577

AC:

13073

AN:

22672

East Asian (EAS)

AF:

0.330

AC:

12412

AN:

37564

South Asian (SAS)

AF:

0.552

AC:

41917

AN:

75974

European-Finnish (FIN)

AF:

0.595

AC:

25619

AN:

43044

Middle Eastern (MID)

AF:

0.636

AC:

2385

AN:

3750

European-Non Finnish (NFE)

AF:

0.592

AC:

546287

AN:

922490

Other (OTH)

AF:

0.589

AC:

30849

AN:

52376

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.334

Heterozygous variant carriers

17769

35538

53308

71077

88846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13182

26364

39546

52728

65910

<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:

0.623

AC:

93333

AN:

149764

Hom.:

29647

Cov.:

AF XY:

0.622

AC XY:

45475

AN XY:

73086

show subpopulations

African (AFR)

AF:

0.718

AC:

29111

AN:

40566

American (AMR)

AF:

0.666

AC:

10063

AN:

15102

Ashkenazi Jewish (ASJ)

AF:

0.559

AC:

1926

AN:

3446

East Asian (EAS)

AF:

0.324

AC:

1637

AN:

5058

South Asian (SAS)

AF:

0.542

AC:

2568

AN:

4740

European-Finnish (FIN)

AF:

0.616

AC:

6420

AN:

10422

Middle Eastern (MID)

AF:

0.658

AC:

192

AN:

292

European-Non Finnish (NFE)

AF:

0.590

AC:

39623

AN:

67178

Other (OTH)

AF:

0.587

AC:

1213

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

1658

3315

4973

6630

8288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

744

1488

2232

2976

3720

<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:

0.611

Hom.:

4789

Bravo

AF:

0.628

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Isolated lutropin deficiency

Benign:3

Jul 28, 2017

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 19, 2021

Genome-Nilou Lab

Significance: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

-0.91

CADD

Benign

0.0070

(source)

DANN

Benign

0.65

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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