Variant 19-49016209-A-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.285T>C(p.Gly95=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 1,612,380 control chromosomes in the GnomAD database, including 302,154 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 32010 hom., cov: 33)

Exomes 𝑓: 0.61 ( 270144 hom. )

Consequence

LHB
NM_000894.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.15

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=-0.88).

BP6

Variant 19-49016209-A-G is Benign according to our data. Variant chr19-49016209-A-G is described in ClinVar as [Benign]. Clinvar id is 1258177.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-49016209-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.719 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.285T>C	p.Gly95=	synonymous_variant	3/3	ENST00000649238.3	NP_000885.1
LHB	XM_047438832.1 linkuse as main transcript	c.333T>C	p.Gly111=	synonymous_variant	2/2		XP_047294788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHB	ENST00000649238.3 linkuse as main transcript	c.285T>C	p.Gly95=	synonymous_variant	3/3		NM_000894.3	ENSP00000497294	P1
LHB	ENST00000649284.1 linkuse as main transcript	n.376T>C		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.644

AC:

97821

AN:

152010

Hom.:

31980

Cov.:

show subpopulations

Gnomad AFR

AF:

0.726

Gnomad AMI

AF:

0.656

Gnomad AMR

AF:

0.698

Gnomad ASJ

AF:

0.577

Gnomad EAS

AF:

0.333

Gnomad SAS

AF:

0.551

Gnomad FIN

AF:

0.627

Gnomad MID

AF:

0.677

Gnomad NFE

AF:

0.618

Gnomad OTH

AF:

0.621

GnomAD3 exomes

AF:

0.610

AC:

153036

AN:

251046

Hom.:

47984

AF XY:

0.602

AC XY:

81768

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.730

Gnomad AMR exome

AF:

0.726

Gnomad ASJ exome

AF:

0.583

Gnomad EAS exome

AF:

0.325

Gnomad SAS exome

AF:

0.554

Gnomad FIN exome

AF:

0.634

Gnomad NFE exome

AF:

0.616

Gnomad OTH exome

AF:

0.609

GnomAD4 exome

AF:

0.605

AC:

883643

AN:

1460250

Hom.:

270144

Cov.:

109

AF XY:

0.603

AC XY:

438160

AN XY:

726436

show subpopulations

Gnomad4 AFR exome

AF:

0.738

Gnomad4 AMR exome

AF:

0.721

Gnomad4 ASJ exome

AF:

0.587

Gnomad4 EAS exome

AF:

0.342

Gnomad4 SAS exome

AF:

0.555

Gnomad4 FIN exome

AF:

0.636

Gnomad4 NFE exome

AF:

0.609

Gnomad4 OTH exome

AF:

0.605

GnomAD4 genome

AF:

0.644

AC:

97897

AN:

152130

Hom.:

32010

Cov.:

AF XY:

0.642

AC XY:

47772

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.725

Gnomad4 AMR

AF:

0.698

Gnomad4 ASJ

AF:

0.577

Gnomad4 EAS

AF:

0.332

Gnomad4 SAS

AF:

0.551

Gnomad4 FIN

AF:

0.627

Gnomad4 NFE

AF:

0.618

Gnomad4 OTH

AF:

0.618

Alfa

AF:

0.621

Hom.:

37342

Bravo

AF:

0.647

Asia WGS

AF:

0.451

AC:

1573

AN:

3478

EpiCase

AF:

0.620

EpiControl

AF:

0.618

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

Isolated lutropin deficiency

Benign:1

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

-0.88

CADD

Benign

0.012

DANN

Benign

0.48

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