rs4952923

Variant names:

• chr2-48734858-A-G
• rs4952923
• NM_000233.4:c.162-3560T>C

Variant summary

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

The NM_000233.4(LHCGR):​c.162-3560T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,210 control chromosomes in the GnomAD database, including 2,776 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 0.17 (2776 hom., cov: 33)
• Consequence: LHCGR NM_000233.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHCGR	NM_000233.4	c.162-3560T>C		intron_variant	Intron 1 of 10	ENST00000294954.12	NP_000224.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHCGR	ENST00000294954.12	c.162-3560T>C		intron_variant	Intron 1 of 10	1	NM_000233.4	ENSP00000294954.6
ENSG00000279956	ENST00000602369.3	n.162-3560T>C		intron_variant	Intron 1 of 12	5		ENSP00000473498.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25471 AN: 152090 Hom.: 2772 Cov.: 33

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.0679

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.167 AC: 25472 AN: 152210 Hom.: 2776 Cov.: 33 AF XY: 0.169 AC XY: 12553 AN XY: 74428

African (AFR) AF: 0.0448 AC: 1862 AN: 41564

American (AMR) AF: 0.268 AC: 4096 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 495 AN: 3466

East Asian (EAS) AF: 0.337 AC: 1743 AN: 5172

South Asian (SAS) AF: 0.0675 AC: 326 AN: 4828

European-Finnish (FIN) AF: 0.214 AC: 2263 AN: 10594

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14062 AN: 67978

Other (OTH) AF: 0.168 AC: 355 AN: 2112

Alfa AF: 0.198 Hom.: 604

Bravo AF: 0.172

Asia WGS AF: 0.171 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.081
DANN	Benign	0.76
PhyloP100		-1.1
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: rs4952923; hg19: chr2-48961997;