2-48747495-G-T

Position:

• chr2-48747495-G-T

Variant summary

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

The ENST00000294954.12(LHCGR):​c.161+8016C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,044 control chromosomes in the GnomAD database, including 7,172 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 0.28 (7172 hom., cov: 32)
• Consequence: LHCGR ENST00000294954.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHCGR	NM_000233.4	c.161+8016C>A		intron_variant		ENST00000294954.12	NP_000224.2
STON1-GTF2A1L	NM_001198593.2	c.3442-28785G>T		intron_variant			NP_001185522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHCGR	ENST00000294954.12	c.161+8016C>A		intron_variant		1	NM_000233.4	ENSP00000294954	A2

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42801 AN: 151926 Hom.: 7155 Cov.: 32

Gnomad AFR AF: 0.0988

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.282 AC: 42833 AN: 152044 Hom.: 7172 Cov.: 32 AF XY: 0.283 AC XY: 21057 AN XY: 74288

Gnomad4 AFR AF: 0.0988

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.315

Alfa AF: 0.229 Hom.: 776

Bravo AF: 0.279

Asia WGS AF: 0.348 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.51

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: rs35960650; hg19: chr2-48974634;