Genetic Variant NM_000233.4:c.162-6585T>G (chr2-48737883-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000233.4(LHCGR):c.162-6585T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,212 control chromosomes in the GnomAD database, including 3,889 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 0.22 ( 3889 hom., cov: 33)

Consequence

LHCGR
NM_000233.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.99

Publications

6 publications found

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:

ENSG00000279956 (HGNC:):

ENSG00000279956 links:

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]

STON1-GTF2A1L links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHCGR	NM_000233.4 link	c.162-6585T>G		intron_variant	Intron 1 of 10	ENST00000294954.12	NP_000224.2	P22888-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHCGR	ENST00000294954.12 link	c.162-6585T>G		intron_variant	Intron 1 of 10	1	NM_000233.4	ENSP00000294954.6		P22888-1
ENSG00000279956	ENST00000602369.3 link	n.162-6585T>G		intron_variant	Intron 1 of 12	5		ENSP00000473498.1		R4GN57

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33108

AN:

152094

Hom.:

3894

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.352

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.299

Gnomad EAS

AF:

0.0110

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.238

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

GnomAD4 genome

AF:

0.217

AC:

33103

AN:

152212

Hom.:

3889

Cov.:

AF XY:

0.209

AC XY:

15566

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.187

AC:

7754

AN:

41548

American (AMR)

AF:

0.183

AC:

2808

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.299

AC:

1036

AN:

3464

East Asian (EAS)

AF:

0.0110

AC:

AN:

5186

South Asian (SAS)

AF:

0.119

AC:

572

AN:

4824

European-Finnish (FIN)

AF:

0.191

AC:

2025

AN:

10598

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.264

AC:

17942

AN:

67964

Other (OTH)

AF:

0.236

AC:

498

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1322

2644

3966

5288

6610

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

342

684

1026

1368

1710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.251

Hom.:

8504

Bravo

AF:

0.216

Asia WGS

AF:

0.0870

AC:

305

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.8

(source)

DANN

Benign

0.74

PhyloP100

2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over