19-49016819-C-T

Position:

• chr19-49016819-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.67

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHB	NM_000894.3	c.16-105G>A		intron_variant		ENST00000649238.3	NP_000885.1
LHB	XM_047438832.1	c.-42G>A		5_prime_UTR_variant	1/2		XP_047294788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHB	ENST00000649238.3	c.16-105G>A		intron_variant			NM_000894.3	ENSP00000497294.2
LHB	ENST00000649284.1	n.2G>A		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.901 AC: 135903 AN: 150802 Hom.: 61493 Cov.: 28

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

GnomAD3 exomes AF: 0.898 AC: 184962 AN: 205910 Hom.: 83520 AF XY: 0.897 AC XY: 101388 AN XY: 113016

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 SAS exome AF: 0.959

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.: 92 AF XY: 0.872 AC XY: 619350 AN XY: 710008

Gnomad4 AFR exome AF: 0.962

Gnomad4 AMR exome AF: 0.936

Gnomad4 ASJ exome AF: 0.861

Gnomad4 EAS exome AF: 0.985

Gnomad4 SAS exome AF: 0.958

Gnomad4 FIN exome AF: 0.891

Gnomad4 NFE exome AF: 0.853

Gnomad4 OTH exome AF: 0.881

GnomAD4 genome AF: 0.901 AC: 136021 AN: 150916 Hom.: 61554 Cov.: 28 AF XY: 0.904 AC XY: 66594 AN XY: 73632

Gnomad4 AFR AF: 0.965

Gnomad4 AMR AF: 0.906

Gnomad4 ASJ AF: 0.854

Gnomad4 EAS AF: 0.979

Gnomad4 SAS AF: 0.963

Gnomad4 FIN AF: 0.900

Gnomad4 NFE AF: 0.856

Gnomad4 OTH AF: 0.891

Alfa AF: 0.875 Hom.: 10573

Bravo AF: 0.903

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.0050
DANN	Benign	0.66

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

Other links and lift over

dbSNP: rs3956233; hg19: chr19-49520076;