rs4519576

Variant names:

• chr2-48739007-T-C
• rs4519576
• NM_000233.4:c.162-7709A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000233.4(LHCGR):​c.162-7709A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,192 control chromosomes in the GnomAD database, including 13,091 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (13091 hom., cov: 32)
• Consequence: LHCGR NM_000233.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.503
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000233.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHCGR	NM_000233.4	MANE Select	c.162-7709A>G		intron	N/A	NP_000224.2	P22888-1
	STON1-GTF2A1L	NM_001198593.2		c.3442-37273T>C		intron	N/A	NP_001185522.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHCGR	ENST00000294954.12	TSL:1 MANE Select	c.162-7709A>G		intron	N/A	ENSP00000294954.6	P22888-1
	ENSG00000279956	ENST00000602369.3	TSL:5	n.162-7709A>G		intron	N/A	ENSP00000473498.1	R4GN57
	STON1-GTF2A1L	ENST00000402114.6	TSL:2	c.3442-37273T>C		intron	N/A	ENSP00000385701.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61120 AN: 152074 Hom.: 13085 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.0718

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.445

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.402 AC: 61162 AN: 152192 Hom.: 13091 Cov.: 32 AF XY: 0.393 AC XY: 29235 AN XY: 74398

African (AFR) AF: 0.321 AC: 13354 AN: 41540

American (AMR) AF: 0.344 AC: 5256 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1584 AN: 3472

East Asian (EAS) AF: 0.0720 AC: 373 AN: 5182

South Asian (SAS) AF: 0.433 AC: 2085 AN: 4812

European-Finnish (FIN) AF: 0.361 AC: 3812 AN: 10562

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33195 AN: 68006

Other (OTH) AF: 0.444 AC: 939 AN: 2114

Alfa AF: 0.460 Hom.: 13048

Bravo AF: 0.392

Asia WGS AF: 0.287 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.1
DANN	Benign	0.57
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4519576; hg19: chr2-48966146;