Variant 2-48729373-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000233.4(LHCGR):c.234-146T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 703,872 control chromosomes in the GnomAD database, including 41,053 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.37 ( 11559 hom., cov: 32)

Exomes 𝑓: 0.31 ( 29494 hom. )

Consequence

LHCGR
NM_000233.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.49

Variant links:

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]

LHCGR links:

STON1-GTF2A1L (HGNC:):

STON1-GTF2A1L links:

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]

GTF2A1L links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 2-48729373-A-G is Benign according to our data. Variant chr2-48729373-A-G is described in ClinVar as [Benign]. Clinvar id is 1272187.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LHCGR	NM_000233.4 linkuse as main transcript	c.234-146T>C		intron_variant		ENST00000294954.12
STON1-GTF2A1L	NM_001198593.2 linkuse as main transcript	c.3442-46907A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHCGR	ENST00000294954.12 linkuse as main transcript	c.234-146T>C		intron_variant		1	NM_000233.4	A2	P22888-1

Frequencies

GnomAD3 genomes

AF:

0.369

AC:

56028

AN:

151906

Hom.:

11545

Cov.:

show subpopulations

Gnomad AFR

AF:

0.506

Gnomad AMI

AF:

0.414

Gnomad AMR

AF:

0.468

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.600

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.349

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.334

GnomAD4 exome

AF:

0.306

AC:

168853

AN:

551848

Hom.:

29494

AF XY:

0.298

AC XY:

88940

AN XY:

298604

show subpopulations

Gnomad4 AFR exome

AF:

0.518

Gnomad4 AMR exome

AF:

0.564

Gnomad4 ASJ exome

AF:

0.230

Gnomad4 EAS exome

AF:

0.539

Gnomad4 SAS exome

AF:

0.240

Gnomad4 FIN exome

AF:

0.346

Gnomad4 NFE exome

AF:

0.260

Gnomad4 OTH exome

AF:

0.308

GnomAD4 genome

AF:

0.369

AC:

56075

AN:

152024

Hom.:

11559

Cov.:

AF XY:

0.375

AC XY:

27844

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.505

Gnomad4 AMR

AF:

0.468

Gnomad4 ASJ

AF:

0.215

Gnomad4 EAS

AF:

0.600

Gnomad4 SAS

AF:

0.268

Gnomad4 FIN

AF:

0.349

Gnomad4 NFE

AF:

0.265

Gnomad4 OTH

AF:

0.334

Alfa

AF:

0.276

Hom.:

12676

Bravo

AF:

0.391

Asia WGS

AF:

0.410

AC:

1423

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.33

DANN

Benign

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over