rs7562215

Variant names:

• chr2-48731548-G-T
• rs7562215
• NM_000233.4:c.162-250C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-48731548-G-T
• chr2-48731548-G-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000233.4(LHCGR):​c.162-250C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,050 control chromosomes in the GnomAD database, including 5,000 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (5000 hom., cov: 32)
• Consequence: LHCGR NM_000233.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.181
• Publications: 2 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]

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 2-48731548-G-T is Benign according to our data. Variant chr2-48731548-G-T is described in ClinVar as Benign. ClinVar VariationId is 1231032.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 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.162-250C>A		intron	N/A	NP_000224.2	P22888-1
	STON1-GTF2A1L	NM_001198593.2		c.3442-44732G>T		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.162-250C>A		intron	N/A	ENSP00000294954.6	P22888-1
	ENSG00000279956	ENST00000602369.3	TSL:5	n.162-250C>A		intron	N/A	ENSP00000473498.1	R4GN57
	STON1-GTF2A1L	ENST00000402114.6	TSL:2	c.3442-44732G>T		intron	N/A	ENSP00000385701.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30316 AN: 151932 Hom.: 4990 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0699

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.200 AC: 30363 AN: 152050 Hom.: 5000 Cov.: 32 AF XY: 0.204 AC XY: 15193 AN XY: 74328

African (AFR) AF: 0.440 AC: 18234 AN: 41440

American (AMR) AF: 0.198 AC: 3029 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 272 AN: 3470

East Asian (EAS) AF: 0.179 AC: 924 AN: 5174

South Asian (SAS) AF: 0.189 AC: 911 AN: 4816

European-Finnish (FIN) AF: 0.163 AC: 1723 AN: 10570

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0699 AC: 4752 AN: 67994

Other (OTH) AF: 0.164 AC: 345 AN: 2110

Alfa AF: 0.0804 Hom.: 537

Bravo AF: 0.214

Asia WGS AF: 0.197 AC: 687 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.0
DANN	Benign	0.43
PhyloP100		0.18
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: rs7562215; hg19: chr2-48958687;