2-48735152-G-T

Position:

• chr2-48735152-G-T

Variant summary

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

The NM_000233.4(LHCGR):​c.162-3854C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,148 control chromosomes in the GnomAD database, including 3,627 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 0.21 (3627 hom., cov: 33)
• Consequence: LHCGR NM_000233.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.444

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LHCGR	NM_000233.4	c.162-3854C>A		intron_variant		ENST00000294954.12
STON1-GTF2A1L	NM_001198593.2	c.3442-41128G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHCGR	ENST00000294954.12	c.162-3854C>A		intron_variant		1	NM_000233.4	A2

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31960 AN: 152030 Hom.: 3625 Cov.: 33

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.210 AC: 31979 AN: 152148 Hom.: 3627 Cov.: 33 AF XY: 0.202 AC XY: 15048 AN XY: 74402

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.230

Alfa AF: 0.226 Hom.: 4173

Bravo AF: 0.213

Asia WGS AF: 0.0830 AC: 290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.76
DANN	Benign	0.79

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: rs17326656; hg19: chr2-48962291;