2-48729373-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.234-146T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 703,872 control chromosomes in the GnomAD database, including 41,053 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11559 hom., cov: 32)
Exomes 𝑓: 0.31 ( 29494 hom. )

Consequence

LHCGR
NM_000233.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.49
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 Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
Variant 2-48729373-A-G is Benign according to our data. Variant chr2-48729373-A-G is described in ClinVar as [Benign]. Clinvar id is 1272187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LHCGRNM_000233.4 linkc.234-146T>C intron_variant Intron 2 of 10 ENST00000294954.12 NP_000224.2 P22888-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LHCGRENST00000294954.12 linkc.234-146T>C intron_variant Intron 2 of 10 1 NM_000233.4 ENSP00000294954.6 P22888-1
ENSG00000279956ENST00000602369.3 linkn.233+1854T>C intron_variant Intron 2 of 12 5 ENSP00000473498.1 R4GN57

Frequencies

GnomAD3 genomes
AF:
0.369
AC:
56028
AN:
151906
Hom.:
11545
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.506
Gnomad AMI
AF:
0.414
Gnomad AMR
AF:
0.468
Gnomad ASJ
AF:
0.215
Gnomad EAS
AF:
0.600
Gnomad SAS
AF:
0.269
Gnomad FIN
AF:
0.349
Gnomad MID
AF:
0.184
Gnomad NFE
AF:
0.265
Gnomad OTH
AF:
0.334
GnomAD4 exome
AF:
0.306
AC:
168853
AN:
551848
Hom.:
29494
AF XY:
0.298
AC XY:
88940
AN XY:
298604
show subpopulations
Gnomad4 AFR exome
AF:
0.518
Gnomad4 AMR exome
AF:
0.564
Gnomad4 ASJ exome
AF:
0.230
Gnomad4 EAS exome
AF:
0.539
Gnomad4 SAS exome
AF:
0.240
Gnomad4 FIN exome
AF:
0.346
Gnomad4 NFE exome
AF:
0.260
Gnomad4 OTH exome
AF:
0.308
GnomAD4 genome
AF:
0.369
AC:
56075
AN:
152024
Hom.:
11559
Cov.:
32
AF XY:
0.375
AC XY:
27844
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.505
Gnomad4 AMR
AF:
0.468
Gnomad4 ASJ
AF:
0.215
Gnomad4 EAS
AF:
0.600
Gnomad4 SAS
AF:
0.268
Gnomad4 FIN
AF:
0.349
Gnomad4 NFE
AF:
0.265
Gnomad4 OTH
AF:
0.334
Alfa
AF:
0.276
Hom.:
12676
Bravo
AF:
0.391
Asia WGS
AF:
0.410
AC:
1423
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jun 26, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
CADD
Benign
0.33
DANN
Benign
0.81

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: rs11897846; hg19: chr2-48956512; API