chr2-48734257-G-T

Position:

• chr2-48734257-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.162-2959C>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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHCGR	NM_000233.4	c.162-2959C>A		intron_variant		ENST00000294954.12	NP_000224.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHCGR	ENST00000294954.12	c.162-2959C>A		intron_variant		1	NM_000233.4	ENSP00000294954.6
ENSG00000279956	ENST00000602369.3	n.162-2959C>A		intron_variant		5		ENSP00000473498.1

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

Gnomad4 AFR AF: 0.0410

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.0585

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.144

Alfa AF: 0.139 Hom.: 892

Bravo AF: 0.151

Asia WGS AF: 0.159 AC: 553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.34
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs4952922; hg19: chr2-48961396;