dbSNP rs3956233: LHB:c.16-105G>A (chr19-49016819-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000894.3(LHB):c.16-105G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.901 in 150,916 control chromosomes in the GnomAD database, including 61,554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.90 ( 61554 hom., cov: 28)

Exomes 𝑓: 0.87 ( 543068 hom. )

Failed GnomAD Quality Control

Consequence

LHB
NM_000894.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.67

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

hypogonadotropic hypogonadism 23 with or without anosmia
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

LHB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 19-49016819-C-T is Benign according to our data. Variant chr19-49016819-C-T is described in ClinVar as Benign. ClinVar VariationId is 1183687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000894.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHB	NM_000894.3	MANE Select	c.16-105G>A		intron	N/A	NP_000885.1	P01229

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHB	ENST00000649238.3	MANE Select	c.16-105G>A		intron	N/A	ENSP00000497294.2	P01229
	LHB	ENST00000649284.1		n.2G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.901

AC:

135903

AN:

150802

Hom.:

61493

Cov.:

show subpopulations

Gnomad AFR

AF:

0.965

Gnomad AMI

AF:

0.821

Gnomad AMR

AF:

0.906

Gnomad ASJ

AF:

0.854

Gnomad EAS

AF:

0.979

Gnomad SAS

AF:

0.963

Gnomad FIN

AF:

0.900

Gnomad MID

AF:

0.847

Gnomad NFE

AF:

0.856

Gnomad OTH

AF:

0.890

GnomAD2 exomes

AF:

0.898

AC:

184962

AN:

205910

AF XY:

0.897

show subpopulations

Gnomad AFR exome

AF:

0.971

Gnomad AMR exome

AF:

0.939

Gnomad ASJ exome

AF:

0.858

Gnomad EAS exome

AF:

0.976

Gnomad FIN exome

AF:

0.876

Gnomad NFE exome

AF:

0.850

Gnomad OTH exome

AF:

0.871

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.870

AC:

1244580

AN:

1430078

Hom.:

543068

Cov.:

AF XY:

0.872

AC XY:

619350

AN XY:

710008

show subpopulations

African (AFR)

AF:

0.962

AC:

31526

AN:

32768

American (AMR)

AF:

0.936

AC:

39529

AN:

42226

Ashkenazi Jewish (ASJ)

AF:

0.861

AC:

21826

AN:

25356

East Asian (EAS)

AF:

0.985

AC:

38773

AN:

39368

South Asian (SAS)

AF:

0.958

AC:

81444

AN:

85048

European-Finnish (FIN)

AF:

0.891

AC:

38664

AN:

43384

Middle Eastern (MID)

AF:

0.873

AC:

3542

AN:

4058

European-Non Finnish (NFE)

AF:

0.853

AC:

937026

AN:

1098552

Other (OTH)

AF:

0.881

AC:

52250

AN:

59318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

7161

14322

21482

28643

35804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21068

42136

63204

84272

105340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.901

AC:

136021

AN:

150916

Hom.:

61554

Cov.:

AF XY:

0.904

AC XY:

66594

AN XY:

73632

show subpopulations

African (AFR)

AF:

0.965

AC:

39446

AN:

40874

American (AMR)

AF:

0.906

AC:

13772

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.854

AC:

2953

AN:

3458

East Asian (EAS)

AF:

0.979

AC:

5025

AN:

5132

South Asian (SAS)

AF:

0.963

AC:

4597

AN:

4772

European-Finnish (FIN)

AF:

0.900

AC:

9436

AN:

10482

Middle Eastern (MID)

AF:

0.836

AC:

244

AN:

292

European-Non Finnish (NFE)

AF:

0.856

AC:

57937

AN:

67702

Other (OTH)

AF:

0.891

AC:

1864

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

571

1141

1712

2282

2853

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

892

1784

2676

3568

4460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.875

Hom.:

10573

Bravo

AF:

0.903

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.0050

(source)

DANN

Benign

0.66

PhyloP100

-2.7

PromoterAI

0.034

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over