rs1800447

Variant names:

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000894.3(LHB):c.82T>C(p.Trp28Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0756 in 1,608,732 control chromosomes in the GnomAD database, including 5,114 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.075 ( 484 hom., cov: 31)

Exomes 𝑓: 0.076 ( 4630 hom. )

Consequence

LHB
NM_000894.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.604

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005592197).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHB	NM_000894.3 link	c.82T>C	p.Trp28Arg	missense_variant	Exon 2 of 3	ENST00000649238.3	NP_000885.1	P01229A0A0F7RQE6
LHB	XM_047438832.1 link	c.130T>C	p.Trp44Arg	missense_variant	Exon 1 of 2		XP_047294788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHB	ENST00000649238.3 link	c.82T>C	p.Trp28Arg	missense_variant	Exon 2 of 3		NM_000894.3	ENSP00000497294.2		P01229
LHB	ENST00000649284.1 link	n.173T>C		non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0754

AC:

11386

AN:

150980

Hom.:

481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0583

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.0677

Gnomad ASJ

AF:

0.0652

Gnomad EAS

AF:

0.0528

Gnomad SAS

AF:

0.0259

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0831

Gnomad OTH

AF:

0.0816

GnomAD3 exomes

AF:

0.0648

AC:

15994

AN:

246848

Hom.:

694

AF XY:

0.0642

AC XY:

8590

AN XY:

133756

show subpopulations

Gnomad AFR exome

AF:

0.0509

Gnomad AMR exome

AF:

0.0413

Gnomad ASJ exome

AF:

0.0551

Gnomad EAS exome

AF:

0.0585

Gnomad SAS exome

AF:

0.0277

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.0783

Gnomad OTH exome

AF:

0.0740

GnomAD4 exome

AF:

0.0757

AC:

110271

AN:

1457636

Hom.:

4630

Cov.:

135

AF XY:

0.0750

AC XY:

54362

AN XY:

725230

show subpopulations

Gnomad4 AFR exome

AF:

0.0584

Gnomad4 AMR exome

AF:

0.0449

Gnomad4 ASJ exome

AF:

0.0605

Gnomad4 EAS exome

AF:

0.0564

Gnomad4 SAS exome

AF:

0.0280

Gnomad4 FIN exome

AF:

0.131

Gnomad4 NFE exome

AF:

0.0795

Gnomad4 OTH exome

AF:

0.0754

GnomAD4 genome

AF:

0.0755

AC:

11406

AN:

151096

Hom.:

484

Cov.:

AF XY:

0.0753

AC XY:

5557

AN XY:

73796

show subpopulations

Gnomad4 AFR

AF:

0.0586

Gnomad4 AMR

AF:

0.0675

Gnomad4 ASJ

AF:

0.0652

Gnomad4 EAS

AF:

0.0533

Gnomad4 SAS

AF:

0.0257

Gnomad4 FIN

AF:

0.135

Gnomad4 NFE

AF:

0.0831

Gnomad4 OTH

AF:

0.0831

Alfa

AF:

0.0709

Hom.:

142

Bravo

AF:

0.0726

TwinsUK

AF:

0.0636

AC:

236

ALSPAC

AF:

0.0734

AC:

283

ESP6500AA

AF:

0.0431

AC:

190

ESP6500EA

AF:

0.0747

AC:

642

ExAC

AF:

0.0705

AC:

8558

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 7586598, 25111116, 19890021, 7714098, 22108961, 23725475, 7904610) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.0

DANN

Benign

0.56

DEOGEN2

Benign

0.38

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0038

LIST_S2

Benign

0.061

.;T

MetaRNN

Benign

0.0056

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.8

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

0.24

N;.

REVEL

Benign

0.17

Sift

Benign

0.39

T;.

Sift4G

Benign

0.40

T;.

Polyphen

0.0

B;B

Vest4

0.010

MutPred

0.16

Gain of disorder (P = 0.0104);Gain of disorder (P = 0.0104);

MPC

0.13

ClinPred

0.0012

GERP RS

0.27

Varity_R

0.066

gMVP

0.67

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

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