Variant rs4002462 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.16-26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 1,532,984 control chromosomes in the GnomAD database, including 254,672 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 29273 hom., cov: 29)

Exomes 𝑓: 0.56 ( 225399 hom. )

Consequence

LHB
NM_000894.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.521

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=-0.93).

BP6

Variant 19-49016740-A-G is Benign according to our data. Variant chr19-49016740-A-G is described in ClinVar as [Benign]. Clinvar id is 518304.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-49016740-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	Protein	UniProt
LHB	NM_000894.3 linkuse as main transcript	c.16-26T>C		intron_variant		ENST00000649238.3	NP_000885.1
LHB	XM_047438832.1 linkuse as main transcript	c.38T>C	p.Leu13Pro	missense_variant	1/2		XP_047294788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHB	ENST00000649238.3 linkuse as main transcript	c.16-26T>C		intron_variant			NM_000894.3	ENSP00000497294	P1
LHB	ENST00000649284.1 linkuse as main transcript	n.81T>C		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes

AF:

0.617

AC:

92732

AN:

150292

Hom.:

29242

Cov.:

show subpopulations

Gnomad AFR

AF:

0.717

Gnomad AMI

AF:

0.655

Gnomad AMR

AF:

0.665

Gnomad ASJ

AF:

0.559

Gnomad EAS

AF:

0.326

Gnomad SAS

AF:

0.528

Gnomad FIN

AF:

0.576

Gnomad MID

AF:

0.668

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.590

GnomAD3 exomes

AF:

0.573

AC:

131038

AN:

228628

Hom.:

40131

AF XY:

0.565

AC XY:

69884

AN XY:

123732

show subpopulations

Gnomad AFR exome

AF:

0.722

Gnomad AMR exome

AF:

0.698

Gnomad ASJ exome

AF:

0.555

Gnomad EAS exome

AF:

0.315

Gnomad SAS exome

AF:

0.523

Gnomad FIN exome

AF:

0.560

Gnomad NFE exome

AF:

0.573

Gnomad OTH exome

AF:

0.571

GnomAD4 exome

AF:

0.563

AC:

778687

AN:

1382572

Hom.:

225399

Cov.:

AF XY:

0.562

AC XY:

385011

AN XY:

685618

show subpopulations

Gnomad4 AFR exome

AF:

0.738

Gnomad4 AMR exome

AF:

0.700

Gnomad4 ASJ exome

AF:

0.563

Gnomad4 EAS exome

AF:

0.339

Gnomad4 SAS exome

AF:

0.525

Gnomad4 FIN exome

AF:

0.585

Gnomad4 NFE exome

AF:

0.562

Gnomad4 OTH exome

AF:

0.568

GnomAD4 genome

AF:

0.617

AC:

92807

AN:

150412

Hom.:

29273

Cov.:

AF XY:

0.615

AC XY:

45095

AN XY:

73350

show subpopulations

Gnomad4 AFR

AF:

0.717

Gnomad4 AMR

AF:

0.665

Gnomad4 ASJ

AF:

0.559

Gnomad4 EAS

AF:

0.325

Gnomad4 SAS

AF:

0.529

Gnomad4 FIN

AF:

0.576

Gnomad4 NFE

AF:

0.583

Gnomad4 OTH

AF:

0.587

Alfa

AF:

0.599

Hom.:

5002

Bravo

AF:

0.623

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, 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	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.4

DANN

Benign

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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