2-48734257-G-T

Variant names:

• chr2-48734257-G-T
• rs4952922
• NM_000233.4:c.162-2959C>A

Variant summary

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

The NM_000233.4(LHCGR):​c.162-2959C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,118 control chromosomes in the GnomAD database, including 2,176 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 0.15 (2176 hom., cov: 32)
• Consequence: LHCGR NM_000233.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358
• Publications: 1 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.305 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHCGR	NM_000233.4	MANE Select	c.162-2959C>A		intron	N/A	NP_000224.2
	STON1-GTF2A1L	NM_001198593.2		c.3442-42023G>T		intron	N/A	NP_001185522.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHCGR	ENST00000294954.12	TSL:1 MANE Select	c.162-2959C>A		intron	N/A	ENSP00000294954.6
	ENSG00000279956	ENST00000602369.3	TSL:5	n.162-2959C>A		intron	N/A	ENSP00000473498.1
	STON1-GTF2A1L	ENST00000402114.6	TSL:2	c.3442-42023G>T		intron	N/A	ENSP00000385701.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22355 AN: 152000 Hom.: 2170 Cov.: 32

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.0591

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.147 AC: 22362 AN: 152118 Hom.: 2176 Cov.: 32 AF XY: 0.149 AC XY: 11047 AN XY: 74370

African (AFR) AF: 0.0410 AC: 1700 AN: 41502

American (AMR) AF: 0.252 AC: 3845 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 409 AN: 3470

East Asian (EAS) AF: 0.318 AC: 1648 AN: 5180

South Asian (SAS) AF: 0.0585 AC: 282 AN: 4820

European-Finnish (FIN) AF: 0.193 AC: 2039 AN: 10564

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11961 AN: 67996

Other (OTH) AF: 0.144 AC: 305 AN: 2114

Alfa AF: 0.142 Hom.: 999

Bravo AF: 0.151

Asia WGS AF: 0.159 AC: 553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.34
DANN	Benign	0.74
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4952922; hg19: chr2-48961396;