rs786204823

chr19-49016633-TGATGGGGTG-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_000894.3(LHB):c.88_96del(p.His30_Ile32del) variant causes a inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: LHB NM_000894.3 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.04

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000894.3.
• PP5: Variant 19-49016633-TGATGGGGTG-T is Pathogenic according to our data. Variant chr19-49016633-TGATGGGGTG-T is described in ClinVar as [Pathogenic]. Clinvar id is 189291.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-49016633-TGATGGGGTG-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LHB	NM_000894.3	c.88_96del	p.His30_Ile32del	inframe_deletion	2/3	ENST00000649238.3
LHB	XM_047438832.1	c.136_144del	p.His46_Ile48del	inframe_deletion	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHB	ENST00000649238.3	c.88_96del	p.His30_Ile32del	inframe_deletion	2/3		NM_000894.3	P1
LHB	ENST00000649284.1	n.179_187del		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Isolated lutropin deficiency Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 05, 2009

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs786204823; hg19: chr19-49519890;