chr2-48738464-T-C

Variant names:

• chr2-48738464-T-C
• rs6732721
• NM_000233.4:c.162-7166A>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.162-7166A>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
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 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.162-7166A>G		intron	N/A	NP_000224.2	P22888-1
	STON1-GTF2A1L	NM_001198593.2		c.3442-37816T>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.162-7166A>G		intron	N/A	ENSP00000294954.6	P22888-1
	ENSG00000279956	ENST00000602369.3	TSL:5	n.162-7166A>G		intron	N/A	ENSP00000473498.1	R4GN57
	STON1-GTF2A1L	ENST00000402114.6	TSL:2	c.3442-37816T>C		intron	N/A	ENSP00000385701.1

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

African (AFR) AF: 0.438 AC: 18163 AN: 41434

American (AMR) AF: 0.191 AC: 2919 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3468

East Asian (EAS) AF: 0.268 AC: 1382 AN: 5162

South Asian (SAS) AF: 0.191 AC: 921 AN: 4810

European-Finnish (FIN) AF: 0.132 AC: 1394 AN: 10578

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0626 AC: 4256 AN: 68006

Other (OTH) AF: 0.164 AC: 347 AN: 2110

Alfa AF: 0.101 Hom.: 766

Bravo AF: 0.211

Asia WGS AF: 0.227 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.3
DANN	Benign	0.78
PhyloP100		-0.12
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: rs6732721; hg19: chr2-48965603;