19-49016294-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000894.3(LHB):c.200C>G(p.Ala67Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,611,276 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 34 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 46 hom. )

Consequence

LHB
NM_000894.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.406

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023105145).

BP6

Variant 19-49016294-G-C is Benign according to our data. Variant chr19-49016294-G-C is described in ClinVar as [Benign]. Clinvar id is 781469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0127 (1939/152300) while in subpopulation AFR AF= 0.0441 (1834/41568). AF 95% confidence interval is 0.0424. There are 34 homozygotes in gnomad4. There are 910 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHB	NM_000894.3 link	c.200C>G	p.Ala67Gly	missense_variant	Exon 3 of 3	ENST00000649238.3	NP_000885.1	P01229A0A0F7RQE6
LHB	XM_047438832.1 link	c.248C>G	p.Ala83Gly	missense_variant	Exon 2 of 2		XP_047294788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHB	ENST00000649238.3 link	c.200C>G	p.Ala67Gly	missense_variant	Exon 3 of 3		NM_000894.3	ENSP00000497294.2		P01229
LHB	ENST00000649284.1 link	n.291C>G		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0127

AC:

1932

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0441

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00326

AC:

812

AN:

249432

Hom.:

AF XY:

0.00232

AC XY:

313

AN XY:

135184

show subpopulations

Gnomad AFR exome

AF:

0.0450

Gnomad AMR exome

AF:

0.00177

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000142

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00127

AC:

1855

AN:

1458976

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

768

AN XY:

725878

show subpopulations

Gnomad4 AFR exome

AF:

0.0454

Gnomad4 AMR exome

AF:

0.00174

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000756

Gnomad4 OTH exome

AF:

0.00269

GnomAD4 genome

AF:

0.0127

AC:

1939

AN:

152300

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

910

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0441

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.000688

Hom.:

Bravo

AF:

0.0145

ESP6500AA

AF:

0.0386

AC:

170

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00409

AC:

496

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Apr 29, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.40

CADD

Benign

7.3

DANN

Benign

0.83

DEOGEN2

Uncertain

0.56

D;D

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.58

.;T

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.97

L;L

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.2

N;.

REVEL

Benign

0.17

Sift

Benign

0.26

T;.

Sift4G

Benign

0.44

T;.

Polyphen

0.0010

B;B

Vest4

0.17

MVP

0.72

MPC

0.077

ClinPred

0.0082

GERP RS

2.0

Varity_R

0.076

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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