Variant rs2387588 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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:5

Conservation

PhyloP100: -2.12

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 518301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-49016536-A-G is described in Lovd as [Benign].

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/exons	MANE	UniProt
LHB	NM_000894.3 linkuse as main transcript	c.183+11T>C		intron_variant		ENST00000649238.3
LHB	XM_047438832.1 linkuse as main transcript	c.231+11T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHB	ENST00000649238.3 linkuse as main transcript	c.183+11T>C		intron_variant			NM_000894.3	P1
LHB	ENST00000649284.1 linkuse as main transcript	n.274+11T>C		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes

AF:

0.581

AC:

129397

AN:

222778

Hom.:

40880

AF XY:

0.574

AC XY:

69453

AN XY:

120982

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 SAS exome

AF:

0.548

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

Gnomad4 AFR exome

AF:

0.755

Gnomad4 AMR exome

AF:

0.718

Gnomad4 ASJ exome

AF:

0.577

Gnomad4 EAS exome

AF:

0.330

Gnomad4 SAS exome

AF:

0.552

Gnomad4 FIN exome

AF:

0.595

Gnomad4 NFE exome

AF:

0.592

Gnomad4 OTH exome

AF:

0.589

GnomAD4 genome

AF:

0.623

AC:

93333

AN:

149764

Hom.:

29647

Cov.:

AF XY:

0.622

AC XY:

45475

AN XY:

73086

show subpopulations

Gnomad4 AFR

AF:

0.718

Gnomad4 AMR

AF:

0.666

Gnomad4 ASJ

AF:

0.559

Gnomad4 EAS

AF:

0.324

Gnomad4 SAS

AF:

0.542

Gnomad4 FIN

AF:

0.616

Gnomad4 NFE

AF:

0.590

Gnomad4 OTH

AF:

0.587

Alfa

AF:

0.611

Hom.:

4789

Bravo

AF:

0.628

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Isolated lutropin deficiency

Benign:3

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

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.0070

DANN

Benign

0.65

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