Variant chr19-49016616-G-C 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.114C>G(p.Val38=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 1,587,092 control chromosomes in the GnomAD database, including 258,586 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 22978 hom., cov: 28)

Exomes 𝑓: 0.57 ( 235608 hom. )

Consequence

LHB
NM_000894.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -8.53

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=-0.89).

BP6

Variant 19-49016616-G-C is Benign according to our data. Variant chr19-49016616-G-C is described in ClinVar as [Benign]. Clinvar id is 518303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-49016616-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-8.53 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.618 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.114C>G	p.Val38=	synonymous_variant	2/3	ENST00000649238.3	NP_000885.1
LHB	XM_047438832.1 linkuse as main transcript	c.162C>G	p.Val54=	synonymous_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.114C>G	p.Val38=	synonymous_variant	2/3		NM_000894.3	ENSP00000497294	P1
LHB	ENST00000649284.1 linkuse as main transcript	n.205C>G		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

82086

AN:

150118

Hom.:

22960

Cov.:

show subpopulations

Gnomad AFR

AF:

0.472

Gnomad AMI

AF:

0.650

Gnomad AMR

AF:

0.629

Gnomad ASJ

AF:

0.512

Gnomad EAS

AF:

0.325

Gnomad SAS

AF:

0.520

Gnomad FIN

AF:

0.614

Gnomad MID

AF:

0.624

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.530

GnomAD3 exomes

AF:

0.562

AC:

136387

AN:

242482

Hom.:

40480

AF XY:

0.559

AC XY:

73290

AN XY:

131092

show subpopulations

Gnomad AFR exome

AF:

0.465

Gnomad AMR exome

AF:

0.683

Gnomad ASJ exome

AF:

0.525

Gnomad EAS exome

AF:

0.318

Gnomad SAS exome

AF:

0.521

Gnomad FIN exome

AF:

0.626

Gnomad NFE exome

AF:

0.582

Gnomad OTH exome

AF:

0.564

GnomAD4 exome

AF:

0.566

AC:

813670

AN:

1436860

Hom.:

235608

Cov.:

110

AF XY:

0.565

AC XY:

404184

AN XY:

715066

show subpopulations

Gnomad4 AFR exome

AF:

0.475

Gnomad4 AMR exome

AF:

0.675

Gnomad4 ASJ exome

AF:

0.530

Gnomad4 EAS exome

AF:

0.341

Gnomad4 SAS exome

AF:

0.522

Gnomad4 FIN exome

AF:

0.628

Gnomad4 NFE exome

AF:

0.575

Gnomad4 OTH exome

AF:

0.554

GnomAD4 genome

AF:

0.547

AC:

82145

AN:

150232

Hom.:

22978

Cov.:

AF XY:

0.547

AC XY:

40126

AN XY:

73298

show subpopulations

Gnomad4 AFR

AF:

0.472

Gnomad4 AMR

AF:

0.629

Gnomad4 ASJ

AF:

0.512

Gnomad4 EAS

AF:

0.324

Gnomad4 SAS

AF:

0.521

Gnomad4 FIN

AF:

0.614

Gnomad4 NFE

AF:

0.583

Gnomad4 OTH

AF:

0.527

Alfa

AF:

0.539

Hom.:

6181

Bravo

AF:

0.540

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, 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	- -
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

-0.89

CADD

Benign

0.018

DANN

Benign

0.69

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