chr2-48687549-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000233.4(LHCGR):​c.*148T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.067 in 650,988 control chromosomes in the GnomAD database, including 2,316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1172 hom., cov: 32)
Exomes 𝑓: 0.057 ( 1144 hom. )

Consequence

LHCGR
NM_000233.4 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.197
Variant links:
Genes affected
LHCGR (HGNC:6585): (luteinizing hormone/choriogonadotropin receptor) This gene encodes the receptor for both luteinizing hormone and choriogonadotropin. This receptor belongs to the G-protein coupled receptor 1 family, and its activity is mediated by G proteins which activate adenylate cyclase. Mutations in this gene result in disorders of male secondary sexual character development, including familial male precocious puberty, also known as testotoxicosis, hypogonadotropic hypogonadism, Leydig cell adenoma with precocious puberty, and male pseudohermaphtoditism with Leydig cell hypoplasia. [provided by RefSeq, Jul 2008]
GTF2A1L (HGNC:30727): (general transcription factor IIA subunit 1 like) The assembly and stability of the RNA polymerase II transcription pre-initiation complex on a eukaryotic core promoter involve the effects of transcription factor IIA (TFIIA) on the interaction between TATA-binding protein (TBP) and DNA. This gene encodes a germ cell-specific counterpart of the large (alpha/beta) subunit of general transcription factor TFIIA that is able to stabilize the binding of TBP to DNA and may be uniquely important to testis biology. Alternative splicing for this locus has been observed and two variants, encoding distinct isoforms, have been identified. Co-transcription of this gene and the neighboring upstream gene generates a rare transcript (SALF), which encodes a fusion protein comprised of sequence sharing identity with each individual gene product. [provided by RefSeq, Mar 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 2-48687549-A-G is Benign according to our data. Variant chr2-48687549-A-G is described in ClinVar as [Benign]. Clinvar id is 336455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-48687549-A-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LHCGRNM_000233.4 linkuse as main transcriptc.*148T>C 3_prime_UTR_variant 11/11 ENST00000294954.12
STON1-GTF2A1LNM_001198593.2 linkuse as main transcriptc.3441+15869A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LHCGRENST00000294954.12 linkuse as main transcriptc.*148T>C 3_prime_UTR_variant 11/111 NM_000233.4 A2P22888-1
GTF2A1LENST00000508440.1 linkuse as main transcriptc.276+15869A>G intron_variant 2

Frequencies

GnomAD3 genomes
AF:
0.100
AC:
15246
AN:
152144
Hom.:
1167
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.213
Gnomad AMI
AF:
0.0548
Gnomad AMR
AF:
0.0578
Gnomad ASJ
AF:
0.0392
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.0151
Gnomad FIN
AF:
0.0678
Gnomad MID
AF:
0.0411
Gnomad NFE
AF:
0.0645
Gnomad OTH
AF:
0.0808
GnomAD4 exome
AF:
0.0568
AC:
28338
AN:
498726
Hom.:
1144
Cov.:
6
AF XY:
0.0541
AC XY:
14355
AN XY:
265490
show subpopulations
Gnomad4 AFR exome
AF:
0.211
Gnomad4 AMR exome
AF:
0.0410
Gnomad4 ASJ exome
AF:
0.0440
Gnomad4 EAS exome
AF:
0.000158
Gnomad4 SAS exome
AF:
0.0152
Gnomad4 FIN exome
AF:
0.0647
Gnomad4 NFE exome
AF:
0.0629
Gnomad4 OTH exome
AF:
0.0655
GnomAD4 genome
AF:
0.100
AC:
15260
AN:
152262
Hom.:
1172
Cov.:
32
AF XY:
0.0956
AC XY:
7119
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.213
Gnomad4 AMR
AF:
0.0576
Gnomad4 ASJ
AF:
0.0392
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.0151
Gnomad4 FIN
AF:
0.0678
Gnomad4 NFE
AF:
0.0645
Gnomad4 OTH
AF:
0.0799
Alfa
AF:
0.0783
Hom.:
141
Bravo
AF:
0.106
Asia WGS
AF:
0.0250
AC:
85
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxAug 12, 2018- -
Hypergonadotropic hypogonadism Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Leydig cell agenesis Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Gonadotropin-independent familial sexual precocity Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.35
DANN
Benign
0.53

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs79248442; hg19: chr2-48914688; API