rs2013040

Variant names:

• chr19-49015983-G-A
• rs2013040
• NM_000894.3:c.*85C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000894.3(LHB):​c.*85C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0767 in 1,614,066 control chromosomes in the GnomAD database, including 5,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (520 hom., cov: 33)
  • Exomes 𝑓: 0.076 (4670 hom.)
• Consequence: LHB NM_000894.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0530
• Publications: 11 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]

RUVBL2 (HGNC:10475): (RuvB like AAA ATPase 2) This gene encodes the second human homologue of the bacterial RuvB gene. Bacterial RuvB protein is a DNA helicase essential for homologous recombination and DNA double-strand break repair. Functional analysis showed that this gene product has both ATPase and DNA helicase activities. This gene is physically linked to the CGB/LHB gene cluster on chromosome 19q13.3, and is very close (55 nt) to the LHB gene, in the opposite orientation. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-49015983-G-A is Benign according to our data. Variant chr19-49015983-G-A is described in CliVar as Benign. Clinvar id is 1261028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHB	NM_000894.3	c.*85C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000649238.3	NP_000885.1
RUVBL2	NM_006666.3	c.*141G>A		downstream_gene_variant		ENST00000595090.6	NP_006657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHB	ENST00000649238.3	c.*85C>T		3_prime_UTR_variant	Exon 3 of 3		NM_000894.3	ENSP00000497294.2
RUVBL2	ENST00000595090.6	c.*141G>A		downstream_gene_variant		1	NM_006666.3	ENSP00000473172.1

Frequencies

GnomAD3 genomes AF: 0.0789 AC: 12003 AN: 152170 Hom.: 517 Cov.: 33

Gnomad AFR AF: 0.0661

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0693

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.0556

Gnomad SAS AF: 0.0267

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0847

Gnomad OTH AF: 0.0860

GnomAD2 exomes AF: 0.0730 AC: 18334 AN: 251226 AF XY: 0.0711

Gnomad AFR exome AF: 0.0638

Gnomad AMR exome AF: 0.0436

Gnomad ASJ exome AF: 0.0585

Gnomad EAS exome AF: 0.0626

Gnomad FIN exome AF: 0.141

Gnomad NFE exome AF: 0.0846

Gnomad OTH exome AF: 0.0810

GnomAD4 exome AF: 0.0764 AC: 111749 AN: 1461778 Hom.: 4670 Cov.: 84 AF XY: 0.0757 AC XY: 55023 AN XY: 727190

African (AFR) AF: 0.0668 AC: 2236 AN: 33478

American (AMR) AF: 0.0456 AC: 2041 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 1588 AN: 26136

East Asian (EAS) AF: 0.0565 AC: 2242 AN: 39700

South Asian (SAS) AF: 0.0280 AC: 2415 AN: 86258

European-Finnish (FIN) AF: 0.141 AC: 7524 AN: 53406

Middle Eastern (MID) AF: 0.0944 AC: 544 AN: 5760

European-Non Finnish (NFE) AF: 0.0797 AC: 88584 AN: 1111928

Other (OTH) AF: 0.0758 AC: 4575 AN: 60390

GnomAD4 genome AF: 0.0790 AC: 12024 AN: 152288 Hom.: 520 Cov.: 33 AF XY: 0.0791 AC XY: 5889 AN XY: 74448

African (AFR) AF: 0.0663 AC: 2754 AN: 41548

American (AMR) AF: 0.0691 AC: 1058 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0660 AC: 229 AN: 3470

East Asian (EAS) AF: 0.0562 AC: 291 AN: 5182

South Asian (SAS) AF: 0.0267 AC: 129 AN: 4830

European-Finnish (FIN) AF: 0.139 AC: 1479 AN: 10610

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0847 AC: 5761 AN: 68026

Other (OTH) AF: 0.0874 AC: 185 AN: 2116

Alfa AF: 0.0773 Hom.: 107

Bravo AF: 0.0730

Asia WGS AF: 0.0620 AC: 218 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.87
DANN	Benign	0.72
PhyloP100		0.053
Mutation Taster		=100/0	polymorphism (auto)

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: rs2013040; hg19: chr19-49519240; COSMIC: COSV55485478; COSMIC: COSV55485478;