Variant 19-49015983-G-A 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.*85C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0767 in 1,614,066 control chromosomes in the GnomAD database, including 5,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.079 ( 520 hom., cov: 33)

Exomes 𝑓: 0.076 ( 4670 hom. )

Consequence

LHB
NM_000894.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0530

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:

RUVBL2 (HGNC:10475): (RuvB like AAA ATPase 2) This gene encodes the second human homologue of the bacterial RuvB gene. Bacterial RuvB protein is a DNA helicase essential for homologous recombination and DNA double-strand break repair. Functional analysis showed that this gene product has both ATPase and DNA helicase activities. This gene is physically linked to the CGB/LHB gene cluster on chromosome 19q13.3, and is very close (55 nt) to the LHB gene, in the opposite orientation. [provided by RefSeq, Jul 2008]

RUVBL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 19-49015983-G-A is Benign according to our data. Variant chr19-49015983-G-A is described in ClinVar as [Benign]. Clinvar id is 1261028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0829 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.*85C>T		3_prime_UTR_variant	3/3	ENST00000649238.3	NP_000885.1
RUVBL2	NM_006666.3 linkuse as main transcript			downstream_gene_variant		ENST00000595090.6	NP_006657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHB	ENST00000649238.3 linkuse as main transcript	c.*85C>T		3_prime_UTR_variant	3/3		NM_000894.3	ENSP00000497294	P1
RUVBL2	ENST00000595090.6 linkuse as main transcript			downstream_gene_variant		1	NM_006666.3	ENSP00000473172	P1	Q9Y230-1

Frequencies

GnomAD3 genomes

AF:

0.0789

AC:

12003

AN:

152170

Hom.:

517

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0661

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.0693

Gnomad ASJ

AF:

0.0660

Gnomad EAS

AF:

0.0556

Gnomad SAS

AF:

0.0267

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0847

Gnomad OTH

AF:

0.0860

GnomAD3 exomes

AF:

0.0730

AC:

18334

AN:

251226

Hom.:

780

AF XY:

0.0711

AC XY:

9667

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.0638

Gnomad AMR exome

AF:

0.0436

Gnomad ASJ exome

AF:

0.0585

Gnomad EAS exome

AF:

0.0626

Gnomad SAS exome

AF:

0.0291

Gnomad FIN exome

AF:

0.141

Gnomad NFE exome

AF:

0.0846

Gnomad OTH exome

AF:

0.0810

GnomAD4 exome

AF:

0.0764

AC:

111749

AN:

1461778

Hom.:

4670

Cov.:

AF XY:

0.0757

AC XY:

55023

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.0668

Gnomad4 AMR exome

AF:

0.0456

Gnomad4 ASJ exome

AF:

0.0608

Gnomad4 EAS exome

AF:

0.0565

Gnomad4 SAS exome

AF:

0.0280

Gnomad4 FIN exome

AF:

0.141

Gnomad4 NFE exome

AF:

0.0797

Gnomad4 OTH exome

AF:

0.0758

GnomAD4 genome

AF:

0.0790

AC:

12024

AN:

152288

Hom.:

520

Cov.:

AF XY:

0.0791

AC XY:

5889

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0663

Gnomad4 AMR

AF:

0.0691

Gnomad4 ASJ

AF:

0.0660

Gnomad4 EAS

AF:

0.0562

Gnomad4 SAS

AF:

0.0267

Gnomad4 FIN

AF:

0.139

Gnomad4 NFE

AF:

0.0847

Gnomad4 OTH

AF:

0.0874

Alfa

AF:

0.0780

Hom.:

104

Bravo

AF:

0.0730

Asia WGS

AF:

0.0620

AC:

218

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.87

DANN

Benign

0.72

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