Variant 19-49016598-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000894.3(LHB):c.132A>C(p.Pro44Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 1,597,094 control chromosomes in the GnomAD database, including 211,537 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23023 hom., cov: 28)

Exomes 𝑓: 0.50 ( 188514 hom. )

Consequence

LHB
NM_000894.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.17

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BP6

Variant 19-49016598-T-G is Benign according to our data. Variant chr19-49016598-T-G is described in ClinVar as [Benign]. Clinvar id is 518302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-49016598-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-5.18 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHB	NM_000894.3 link	c.132A>C	p.Pro44Pro	synonymous_variant	2/3	ENST00000649238.3	NP_000885.1	P01229A0A0F7RQE6
LHB	XM_047438832.1 link	c.180A>C	p.Pro60Pro	synonymous_variant	1/2		XP_047294788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHB	ENST00000649238.3 link	c.132A>C	p.Pro44Pro	synonymous_variant	2/3		NM_000894.3	ENSP00000497294.2		P01229
LHB	ENST00000649284.1 link	n.223A>C		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes

AF:

0.546

AC:

81979

AN:

150144

Hom.:

23001

Cov.:

show subpopulations

Gnomad AFR

AF:

0.656

Gnomad AMI

AF:

0.543

Gnomad AMR

AF:

0.598

Gnomad ASJ

AF:

0.493

Gnomad EAS

AF:

0.272

Gnomad SAS

AF:

0.503

Gnomad FIN

AF:

0.476

Gnomad MID

AF:

0.561

Gnomad NFE

AF:

0.507

Gnomad OTH

AF:

0.510

GnomAD3 exomes

AF:

0.518

AC:

128825

AN:

248844

Hom.:

34800

AF XY:

0.511

AC XY:

68895

AN XY:

134780

show subpopulations

Gnomad AFR exome

AF:

0.665

Gnomad AMR exome

AF:

0.663

Gnomad ASJ exome

AF:

0.508

Gnomad EAS exome

AF:

0.262

Gnomad SAS exome

AF:

0.503

Gnomad FIN exome

AF:

0.490

Gnomad NFE exome

AF:

0.505

Gnomad OTH exome

AF:

0.505

GnomAD4 exome

AF:

0.504

AC:

729762

AN:

1446832

Hom.:

188514

Cov.:

AF XY:

0.503

AC XY:

362326

AN XY:

720008

show subpopulations

Gnomad4 AFR exome

AF:

0.670

Gnomad4 AMR exome

AF:

0.655

Gnomad4 ASJ exome

AF:

0.510

Gnomad4 EAS exome

AF:

0.285

Gnomad4 SAS exome

AF:

0.505

Gnomad4 FIN exome

AF:

0.489

Gnomad4 NFE exome

AF:

0.502

Gnomad4 OTH exome

AF:

0.507

GnomAD4 genome

AF:

0.546

AC:

82032

AN:

150262

Hom.:

23023

Cov.:

AF XY:

0.545

AC XY:

39925

AN XY:

73290

show subpopulations

Gnomad4 AFR

AF:

0.655

Gnomad4 AMR

AF:

0.598

Gnomad4 ASJ

AF:

0.493

Gnomad4 EAS

AF:

0.271

Gnomad4 SAS

AF:

0.503

Gnomad4 FIN

AF:

0.476

Gnomad4 NFE

AF:

0.507

Gnomad4 OTH

AF:

0.505

Alfa

AF:

0.484

Hom.:

5017

Bravo

AF:

0.556

EpiCase

AF:

0.515

EpiControl

AF:

0.506

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Isolated lutropin deficiency

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Jul 28, 2017	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.016

DANN

Benign

0.32

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