rs4073366

Variant names:

• chr2-48755483-C-G
• rs4073366
• NM_000233.4:c.161+28G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-48755483-C-G
• chr2-48755483-C-A
• chr2-48755483-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000233.4(LHCGR):​c.161+28G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,431,042 control chromosomes in the GnomAD database, including 21,445 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2275 hom., cov: 32)
  • Exomes 𝑓: 0.16 (19170 hom.)
• Consequence: LHCGR NM_000233.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0630
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-48755483-C-G is Benign according to our data. Variant chr2-48755483-C-G is described in ClinVar as Benign. ClinVar VariationId is 1278671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHCGR	NM_000233.4	MANE Select	c.161+28G>C		intron	N/A	NP_000224.2	P22888-1
	STON1-GTF2A1L	NM_001198593.2		c.3442-20797C>G		intron	N/A	NP_001185522.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHCGR	ENST00000294954.12	TSL:1 MANE Select	c.161+28G>C		intron	N/A	ENSP00000294954.6	P22888-1
	ENSG00000279956	ENST00000602369.3	TSL:5	n.161+28G>C		intron	N/A	ENSP00000473498.1	R4GN57
	STON1-GTF2A1L	ENST00000402114.6	TSL:2	c.3442-20797C>G		intron	N/A	ENSP00000385701.1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24357 AN: 152056 Hom.: 2267 Cov.: 32

Gnomad AFR AF: 0.0979

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.155

GnomAD2 exomes AF: 0.187 AC: 26433 AN: 141026 AF XY: 0.174

Gnomad AFR exome AF: 0.0930

Gnomad AMR exome AF: 0.345

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.337

Gnomad FIN exome AF: 0.181

Gnomad NFE exome AF: 0.165

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.165 AC: 210580 AN: 1278868 Hom.: 19170 Cov.: 18 AF XY: 0.161 AC XY: 102423 AN XY: 634988

African (AFR) AF: 0.0912 AC: 2654 AN: 29086

American (AMR) AF: 0.330 AC: 11372 AN: 34488

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 3047 AN: 23968

East Asian (EAS) AF: 0.289 AC: 10112 AN: 34978

South Asian (SAS) AF: 0.0539 AC: 4100 AN: 76048

European-Finnish (FIN) AF: 0.187 AC: 8589 AN: 45904

Middle Eastern (MID) AF: 0.0741 AC: 291 AN: 3926

European-Non Finnish (NFE) AF: 0.166 AC: 162021 AN: 976734

Other (OTH) AF: 0.156 AC: 8394 AN: 53736

GnomAD4 genome AF: 0.160 AC: 24376 AN: 152174 Hom.: 2275 Cov.: 32 AF XY: 0.162 AC XY: 12022 AN XY: 74386

African (AFR) AF: 0.0978 AC: 4064 AN: 41548

American (AMR) AF: 0.259 AC: 3960 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 414 AN: 3472

East Asian (EAS) AF: 0.324 AC: 1663 AN: 5136

South Asian (SAS) AF: 0.0581 AC: 280 AN: 4822

European-Finnish (FIN) AF: 0.196 AC: 2078 AN: 10596

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11430 AN: 67986

Other (OTH) AF: 0.153 AC: 324 AN: 2114

Alfa AF: 0.158 Hom.: 406

Bravo AF: 0.167

Asia WGS AF: 0.169 AC: 586 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.3
DANN	Benign	0.34
PhyloP100		0.063
PromoterAI		0.049	Neutral
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: rs4073366; hg19: chr2-48982622; COSMIC: COSV54301735;