rs4952923

Positions:

• chr2-48734858-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000294954.12(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 ENST00000294954.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LHCGR	NM_000233.4	c.162-3560T>C		intron_variant		ENST00000294954.12	NP_000224.2
STON1-GTF2A1L	NM_001198593.2	c.3442-41422A>G		intron_variant			NP_001185522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHCGR	ENST00000294954.12	c.162-3560T>C		intron_variant		1	NM_000233.4	ENSP00000294954	A2

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

Gnomad4 AFR AF: 0.0448

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.0675

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.168

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

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

Other links and lift over

dbSNP: rs4952923; hg19: chr2-48961997;