19-49017115-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The XM_047438832.1(LHB):c.-338T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 1,613,654 control chromosomes in the GnomAD database, including 291,382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (36518 hom., cov: 33)
  • Exomes 𝑓: 0.59 (254864 hom.)
• Consequence: LHB XM_047438832.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.62

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 19-49017115-A-T is Benign according to our data. Variant chr19-49017115-A-T is described in ClinVar as [Benign]. Clinvar id is 1292721.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LHB	XM_047438832.1	c.-338T>A		5_prime_UTR_variant	1/2
LHB	NM_000894.3			upstream_gene_variant		ENST00000649238.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHB	ENST00000649238.3			upstream_gene_variant			NM_000894.3	P1

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102838 AN: 151992 Hom.: 36470 Cov.: 33

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.635

GnomAD3 exomes AF: 0.604 AC: 151658 AN: 251234 Hom.: 47694 AF XY: 0.592 AC XY: 80367 AN XY: 135786

Gnomad AFR exome AF: 0.902

Gnomad AMR exome AF: 0.716

Gnomad ASJ exome AF: 0.566

Gnomad EAS exome AF: 0.326

Gnomad SAS exome AF: 0.533

Gnomad FIN exome AF: 0.627

Gnomad NFE exome AF: 0.590

Gnomad OTH exome AF: 0.592

GnomAD4 exome AF: 0.586 AC: 855891 AN: 1461542 Hom.: 254864 Cov.: 62 AF XY: 0.583 AC XY: 423914 AN XY: 727088

Gnomad4 AFR exome AF: 0.909

Gnomad4 AMR exome AF: 0.711

Gnomad4 ASJ exome AF: 0.571

Gnomad4 EAS exome AF: 0.342

Gnomad4 SAS exome AF: 0.533

Gnomad4 FIN exome AF: 0.629

Gnomad4 NFE exome AF: 0.581

Gnomad4 OTH exome AF: 0.595

GnomAD4 genome AF: 0.677 AC: 102938 AN: 152112 Hom.: 36518 Cov.: 33 AF XY: 0.674 AC XY: 50104 AN XY: 74354

Gnomad4 AFR AF: 0.894

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.632

Alfa AF: 0.556 Hom.: 3027

Bravo AF: 0.686

Asia WGS AF: 0.454 AC: 1582 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	17
Dann	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3752210; hg19: chr19-49520372; COSMIC: COSV55485532;