2-48747495-G-T

Variant names:

• chr2-48747495-G-T
• rs35960650
• NM_000233.4:c.161+8016C>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.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 NM_000233.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 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.161+8016C>A		intron	N/A	NP_000224.2
	STON1-GTF2A1L	NM_001198593.2		c.3442-28785G>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.161+8016C>A		intron	N/A	ENSP00000294954.6
	ENSG00000279956	ENST00000602369.3	TSL:5	n.161+8016C>A		intron	N/A	ENSP00000473498.1
	STON1-GTF2A1L	ENST00000402114.6	TSL:2	c.3442-28785G>T		intron	N/A	ENSP00000385701.1

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

African (AFR) AF: 0.0988 AC: 4099 AN: 41494

American (AMR) AF: 0.378 AC: 5776 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 903 AN: 3472

East Asian (EAS) AF: 0.398 AC: 2054 AN: 5156

South Asian (SAS) AF: 0.362 AC: 1743 AN: 4812

European-Finnish (FIN) AF: 0.310 AC: 3271 AN: 10560

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23938 AN: 67962

Other (OTH) AF: 0.315 AC: 664 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.51
PhyloP100		0.077
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: rs35960650; hg19: chr2-48974634;