2-48725689-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000233.4(LHCGR):​c.370C>G​(p.Arg124Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,156 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

LHCGR
NM_000233.4 missense

Scores

3
8
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.73
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]
STON1-GTF2A1L (HGNC:30651): (STON1-GTF2A1L readthrough) STON1-GTF2A1L mRNAs are infrequent but naturally occurring read-through products of the neighboring STON1 and GTF2A1L genes. These transcripts encode fusion proteins composed of the vast majority of each of the individual elements, stonin 1 and general transcription factor IIA, 1-like. Alternative splicing results in multiple transcript variants. The significance of these read-through variants and the function of the resulting protein products have not yet been determined. [provided by RefSeq, Oct 2010]
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LHCGRNM_000233.4 linkc.370C>G p.Arg124Gly missense_variant Exon 4 of 11 ENST00000294954.12 NP_000224.2 P22888-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LHCGRENST00000294954.12 linkc.370C>G p.Arg124Gly missense_variant Exon 4 of 11 1 NM_000233.4 ENSP00000294954.6 P22888-1
ENSG00000279956ENST00000602369.3 linkn.295C>G non_coding_transcript_exon_variant Exon 3 of 13 5 ENSP00000473498.1 R4GN57

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460156
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726546
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Pathogenic
0.34
D
BayesDel_noAF
Pathogenic
0.25
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.79
D;.;.;.;.
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.83
T;T;D;D;T
M_CAP
Uncertain
0.13
D
MetaRNN
Uncertain
0.69
D;D;D;D;D
MetaSVM
Uncertain
0.017
D
MutationAssessor
Benign
0.78
N;.;.;.;.
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-2.2
N;D;D;D;D
REVEL
Pathogenic
0.69
Sift
Benign
0.14
T;T;T;T;T
Sift4G
Benign
0.090
T;T;D;D;D
Polyphen
0.77
P;.;.;.;.
Vest4
0.71
MutPred
0.55
Loss of MoRF binding (P = 0.0766);Loss of MoRF binding (P = 0.0766);Loss of MoRF binding (P = 0.0766);Loss of MoRF binding (P = 0.0766);.;
MVP
0.90
MPC
0.19
ClinPred
0.90
D
GERP RS
5.2
Varity_R
0.26
gMVP
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: rs773279269; hg19: chr2-48952828; COSMIC: COSV54296553; COSMIC: COSV54296553; API