rs6755901
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000233.4(LHCGR):c.866+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 1,612,146 control chromosomes in the GnomAD database, including 546,775 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000233.4 splice_region, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LHCGR | ENST00000294954.12 | c.866+8G>A | splice_region_variant, intron_variant | Intron 9 of 10 | 1 | NM_000233.4 | ENSP00000294954.6 | |||
ENSG00000279956 | ENST00000602369.3 | n.*139+8G>A | splice_region_variant, intron_variant | Intron 8 of 12 | 5 | ENSP00000473498.1 |
Frequencies
GnomAD3 genomes AF: 0.806 AC: 122490AN: 152000Hom.: 50033 Cov.: 32
GnomAD3 exomes AF: 0.752 AC: 188938AN: 251182Hom.: 73578 AF XY: 0.764 AC XY: 103721AN XY: 135782
GnomAD4 exome AF: 0.820 AC: 1197202AN: 1460028Hom.: 496692 Cov.: 35 AF XY: 0.820 AC XY: 595777AN XY: 726472
GnomAD4 genome AF: 0.806 AC: 122595AN: 152118Hom.: 50083 Cov.: 32 AF XY: 0.795 AC XY: 59102AN XY: 74360
ClinVar
Submissions by phenotype
not specified Benign:5
- -
- -
- -
- -
- -
not provided Benign:3
- -
- -
- -
Hypergonadotropic hypogonadism Benign:1
- -
Leydig cell agenesis Benign:1
This 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. -
Gonadotropin-independent familial sexual precocity Benign:1
This 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at