rs1056914

Variant names:

• chr19-49016598-T-A
• rs1056914
• NM_000894.3:c.132A>T

Your query was ambiguous. Multiple possible variants found:

• chr19-49016598-T-A
• chr19-49016598-T-G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000894.3(LHB):​c.132A>T​(p.Pro44Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P44P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LHB NM_000894.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.17
• Publications: 10 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP7: Synonymous conserved (PhyloP=-5.18 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHB	NM_000894.3	c.132A>T	p.Pro44Pro	synonymous_variant	Exon 2 of 3	ENST00000649238.3	NP_000885.1
LHB	XM_047438832.1	c.180A>T	p.Pro60Pro	synonymous_variant	Exon 1 of 2		XP_047294788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHB	ENST00000649238.3	c.132A>T	p.Pro44Pro	synonymous_variant	Exon 2 of 3		NM_000894.3	ENSP00000497294.2
LHB	ENST00000649284.1	n.223A>T		non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000274 AC: 4 AN: 1458992 Hom.: 0 Cov.: 95 AF XY: 0.00000276 AC XY: 2 AN XY: 725854

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52762

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4538

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111478

Other (OTH) AF: 0.00 AC: 0 AN: 60216

GnomAD4 genome Cov.: 28

Alfa AF: 0.00 Hom.: 5017

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.015
DANN	Benign	0.28
PhyloP100		-5.2
PromoterAI		0.00040	Neutral

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: rs1056914; hg19: chr19-49519855;