rs6732721

Positions:

• chr2-48738464-T-C

Variant summary

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

The NM_000233.4(LHCGR):​c.162-7166A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,072 control chromosomes in the GnomAD database, including 5,005 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 0.20 (5005 hom., cov: 32)
• Consequence: LHCGR NM_000233.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHCGR	NM_000233.4	c.162-7166A>G		intron_variant		ENST00000294954.12	NP_000224.2
STON1-GTF2A1L	NM_001198593.2	c.3442-37816T>C		intron_variant			NP_001185522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHCGR	ENST00000294954.12	c.162-7166A>G		intron_variant		1	NM_000233.4	ENSP00000294954	A2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29713 AN: 151954 Hom.: 4993 Cov.: 32

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0626

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.196 AC: 29759 AN: 152072 Hom.: 5005 Cov.: 32 AF XY: 0.200 AC XY: 14882 AN XY: 74362

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.0608

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.0626

Gnomad4 OTH AF: 0.164

Alfa AF: 0.100 Hom.: 660

Bravo AF: 0.211

Asia WGS AF: 0.227 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.3
DANN	Benign	0.78

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: rs6732721; hg19: chr2-48965603;