chr2-48755616-G-GGCTGCAGCTGCAGCAGCAGCAGCGGCGGCTGCA

Variant names:

• chr2-48755616-G-GGCTGCAGCTGCAGCAGCAGCAGCGGCGGCTGCA
• rs71245621
• NM_000233.4:c.55_56insTGCAGCCGCCGCTGCTGCTGCTGCAGCTGCAGC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_000233.4(LHCGR):​c.55_56insTGCAGCCGCCGCTGCTGCTGCTGCAGCTGCAGC​(p.Gln18_Pro19insLeuGlnProProLeuLeuLeuLeuGlnLeuGln) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000079 in 151,850 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 25)
  • Exomes 𝑓: 0.00028 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LHCGR NM_000233.4 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830
• Publications: 2 publications found

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]

ENSG00000279956 (HGNC:):

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]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_000233.4

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHCGR	NM_000233.4	c.55_56insTGCAGCCGCCGCTGCTGCTGCTGCAGCTGCAGC	p.Gln18_Pro19insLeuGlnProProLeuLeuLeuLeuGlnLeuGln	conservative_inframe_insertion	Exon 1 of 11	ENST00000294954.12	NP_000224.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHCGR	ENST00000294954.12	c.55_56insTGCAGCCGCCGCTGCTGCTGCTGCAGCTGCAGC	p.Gln18_Pro19insLeuGlnProProLeuLeuLeuLeuGlnLeuGln	conservative_inframe_insertion	Exon 1 of 11	1	NM_000233.4	ENSP00000294954.6
ENSG00000279956	ENST00000602369.3	n.55_56insTGCAGCCGCCGCTGCTGCTGCTGCAGCTGCAGC		non_coding_transcript_exon_variant	Exon 1 of 13	5		ENSP00000473498.1

Frequencies

GnomAD3 genomes AF: 0.0000790 AC: 12 AN: 151850 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000756 AC: 10 AN: 132330 AF XY: 0.0000689

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000284 AC: 392 AN: 1380544 Hom.: 0 Cov.: 34 AF XY: 0.000266 AC XY: 181 AN XY: 681120

African (AFR) AF: 0.0000318 AC: 1 AN: 31426

American (AMR) AF: 0.00 AC: 0 AN: 35580

Ashkenazi Jewish (ASJ) AF: 0.0000400 AC: 1 AN: 25012

East Asian (EAS) AF: 0.00 AC: 0 AN: 35686

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 78996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37214

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4054

European-Non Finnish (NFE) AF: 0.000356 AC: 383 AN: 1075054

Other (OTH) AF: 0.000104 AC: 6 AN: 57522

GnomAD4 genome AF: 0.0000790 AC: 12 AN: 151850 Hom.: 0 Cov.: 25 AF XY: 0.0000270 AC XY: 2 AN XY: 74188

African (AFR) AF: 0.0000484 AC: 2 AN: 41352

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67844

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.083
Mutation Taster		=87/13	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs71245621; hg19: chr2-48982755;