rs4287687

Variant names:

• chr19-49016529-T-A
• rs4287687
• NM_000894.3:c.183+18A>T

Your query was ambiguous. Multiple possible variants found:

• chr19-49016529-T-A
• chr19-49016529-T-C
• chr19-49016529-T-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000894.3(LHB):​c.183+18A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: LHB NM_000894.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 3 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHB	NM_000894.3	c.183+18A>T		intron_variant	Intron 2 of 2	ENST00000649238.3	NP_000885.1
LHB	XM_047438832.1	c.231+18A>T		intron_variant	Intron 1 of 1		XP_047294788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHB	ENST00000649238.3	c.183+18A>T		intron_variant	Intron 2 of 2		NM_000894.3	ENSP00000497294.2
LHB	ENST00000649284.1	n.274+18A>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000370 AC: 1 AN: 270368 Hom.: 0 Cov.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135816

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 2518

American (AMR) AF: 0.00 AC: 0 AN: 4476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5022

East Asian (EAS) AF: 0.00 AC: 0 AN: 17366

South Asian (SAS) AF: 0.00 AC: 0 AN: 18588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 612

European-Non Finnish (NFE) AF: 0.00000494 AC: 1 AN: 202456

Other (OTH) AF: 0.00 AC: 0 AN: 10996

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.017
DANN	Benign	0.53
PhyloP100		-1.2

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

Other links and lift over

dbSNP: rs4287687; hg19: chr19-49519786;