2-48731548-G-T

Position:

• chr2-48731548-G-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LHCGR	NM_000233.4	c.162-250C>A		intron_variant		ENST00000294954.12
STON1-GTF2A1L	NM_001198593.2	c.3442-44732G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHCGR	ENST00000294954.12	c.162-250C>A		intron_variant		1	NM_000233.4	A2

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

Gnomad4 AFR AF: 0.440

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.0784

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.0699

Gnomad4 OTH AF: 0.164

Alfa AF: 0.0774 Hom.: 422

Bravo AF: 0.214

Asia WGS AF: 0.197 AC: 687 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.0
DANN	Benign	0.43

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: rs7562215; hg19: chr2-48958687;