rs34349826

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.104T>C(p.Ile35Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0713 in 1,593,286 control chromosomes in the GnomAD database, including 5,079 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.075 ( 479 hom., cov: 31)

Exomes 𝑓: 0.071 ( 4600 hom. )

Consequence

LHB
NM_000894.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.25

Publications

18 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 (MetaRNN=0.0055906475).

BP6

Variant 19-49016626-A-G is Benign according to our data. Variant chr19-49016626-A-G is described in ClinVar as Benign. ClinVar VariationId is 446194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0808 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000894.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHB	NM_000894.3	MANE Select	c.104T>C	p.Ile35Thr	missense	Exon 2 of 3	NP_000885.1	P01229

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHB	ENST00000649238.3	MANE Select	c.104T>C	p.Ile35Thr	missense	Exon 2 of 3	ENSP00000497294.2	P01229
	LHB	ENST00000649284.1		n.195T>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0746

AC:

11242

AN:

150796

Hom.:

476

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0568

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.0671

Gnomad ASJ

AF:

0.0645

Gnomad EAS

AF:

0.0519

Gnomad SAS

AF:

0.0253

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0827

Gnomad OTH

AF:

0.0806

GnomAD2 exomes

AF:

0.0487

AC:

11597

AN:

238330

AF XY:

0.0471

show subpopulations

Gnomad AFR exome

AF:

0.0426

Gnomad AMR exome

AF:

0.0351

Gnomad ASJ exome

AF:

0.0396

Gnomad EAS exome

AF:

0.0458

Gnomad FIN exome

AF:

0.0777

Gnomad NFE exome

AF:

0.0576

Gnomad OTH exome

AF:

0.0561

GnomAD4 exome

AF:

0.0710

AC:

102352

AN:

1442378

Hom.:

4600

Cov.:

132

AF XY:

0.0703

AC XY:

50450

AN XY:

717722

show subpopulations

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

African (AFR)

AF:

0.0552

AC:

1816

AN:

32892

American (AMR)

AF:

0.0424

AC:

1882

AN:

44424

Ashkenazi Jewish (ASJ)

AF:

0.0567

AC:

1469

AN:

25892

East Asian (EAS)

AF:

0.0536

AC:

2116

AN:

39442

South Asian (SAS)

AF:

0.0262

AC:

2247

AN:

85856

European-Finnish (FIN)

AF:

0.124

AC:

6341

AN:

51116

Middle Eastern (MID)

AF:

0.0776

AC:

360

AN:

4642

European-Non Finnish (NFE)

AF:

0.0745

AC:

81860

AN:

1098430

Other (OTH)

AF:

0.0714

AC:

4261

AN:

59684

⚠️ 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: 0.331

Heterozygous variant carriers

4974

9949

14923

19898

24872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2862

5724

8586

11448

14310

<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:

0.0746

AC:

11260

AN:

150908

Hom.:

479

Cov.:

AF XY:

0.0744

AC XY:

5484

AN XY:

73726

show subpopulations

African (AFR)

AF:

0.0570

AC:

2328

AN:

40860

American (AMR)

AF:

0.0670

AC:

1019

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.0645

AC:

223

AN:

3458

East Asian (EAS)

AF:

0.0525

AC:

269

AN:

5128

South Asian (SAS)

AF:

0.0253

AC:

122

AN:

4820

European-Finnish (FIN)

AF:

0.134

AC:

1399

AN:

10466

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0826

AC:

5591

AN:

67664

Other (OTH)

AF:

0.0821

AC:

172

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.406

Heterozygous variant carriers

440

880

1319

1759

2199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<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:

0.0690

Hom.:

136

TwinsUK

AF:

0.0631

AC:

234

ALSPAC

AF:

0.0734

AC:

283

ESP6500AA

AF:

0.0177

AC:

ESP6500EA

AF:

0.0337

AC:

290

ExAC

AF:

0.0683

AC:

8297

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.52

DEOGEN2

Benign

0.42

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.58

MetaRNN

Benign

0.0056

MetaSVM

Benign

-0.79

MutationAssessor

Benign

-2.0

PhyloP100

1.3

PrimateAI

Uncertain

0.52

PROVEAN

Benign

4.5

REVEL

Benign

0.24

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.048

MPC

0.094

ClinPred

0.0024

GERP RS

3.1

PromoterAI

-0.0018

Neutral

(source)

Varity_R

0.036

gMVP

0.33

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over