2-48711217-C-T

Variant names:

• chr2-48711217-C-T
• rs7579411
• NM_000233.4:c.606-2195G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000233.4(LHCGR):​c.606-2195G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 152,056 control chromosomes in the GnomAD database, including 20,847 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 0.51 (20847 hom., cov: 32)
• Consequence: LHCGR NM_000233.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHCGR	NM_000233.4	c.606-2195G>A		intron_variant	Intron 7 of 10	ENST00000294954.12	NP_000224.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHCGR	ENST00000294954.12	c.606-2195G>A		intron_variant	Intron 7 of 10	1	NM_000233.4	ENSP00000294954.6
ENSG00000279956	ENST00000602369.3	n.531-2195G>A		intron_variant	Intron 6 of 12	5		ENSP00000473498.1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77336 AN: 151938 Hom.: 20810 Cov.: 32

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.509 AC: 77428 AN: 152056 Hom.: 20847 Cov.: 32 AF XY: 0.510 AC XY: 37887 AN XY: 74312

African (AFR) AF: 0.677 AC: 28085 AN: 41470

American (AMR) AF: 0.457 AC: 6983 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1994 AN: 3472

East Asian (EAS) AF: 0.409 AC: 2112 AN: 5170

South Asian (SAS) AF: 0.637 AC: 3065 AN: 4814

European-Finnish (FIN) AF: 0.418 AC: 4409 AN: 10554

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29163 AN: 67988

Other (OTH) AF: 0.510 AC: 1075 AN: 2108

Alfa AF: 0.458 Hom.: 69164

Bravo AF: 0.514

Asia WGS AF: 0.554 AC: 1925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.093
DANN	Benign	0.51
PhyloP100		-2.1
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: rs7579411; hg19: chr2-48938356;