rs9309153

Positions:

• chr2-48718008-C-T

Variant summary

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

The NM_000233.4(LHCGR):​c.537-3954G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0476 in 151,922 control chromosomes in the GnomAD database, including 243 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 0.048 (243 hom., cov: 30)
• Consequence: LHCGR NM_000233.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166

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:):

GTF2A1L (HGNC:30727): (general transcription factor IIA subunit 1 like) The assembly and stability of the RNA polymerase II transcription pre-initiation complex on a eukaryotic core promoter involve the effects of transcription factor IIA (TFIIA) on the interaction between TATA-binding protein (TBP) and DNA. This gene encodes a germ cell-specific counterpart of the large (alpha/beta) subunit of general transcription factor TFIIA that is able to stabilize the binding of TBP to DNA and may be uniquely important to testis biology. Alternative splicing for this locus has been observed and two variants, encoding distinct isoforms, have been identified. Co-transcription of this gene and the neighboring upstream gene generates a rare transcript (SALF), which encodes a fusion protein comprised of sequence sharing identity with each individual gene product. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LHCGR	NM_000233.4	c.537-3954G>A		intron_variant		ENST00000294954.12
STON1-GTF2A1L	NM_001198593.2	c.3441+46328C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHCGR	ENST00000294954.12	c.537-3954G>A		intron_variant		1	NM_000233.4	A2

Frequencies

GnomAD3 genomes AF: 0.0476 AC: 7228 AN: 151806 Hom.: 244 Cov.: 30

Gnomad AFR AF: 0.0827

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0354

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0517

Gnomad FIN AF: 0.0196

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0362

Gnomad OTH AF: 0.0545

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

GnomAD4 genome AF: 0.0476 AC: 7235 AN: 151922 Hom.: 243 Cov.: 30 AF XY: 0.0471 AC XY: 3498 AN XY: 74254

Gnomad4 AFR AF: 0.0826

Gnomad4 AMR AF: 0.0354

Gnomad4 ASJ AF: 0.0588

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0521

Gnomad4 FIN AF: 0.0196

Gnomad4 NFE AF: 0.0362

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0404 Hom.: 47

Bravo AF: 0.0502

Asia WGS AF: 0.0270 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.66

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: rs9309153; hg19: chr2-48945147;