2-48726070-C-T

Variant names:

• chr2-48726070-C-T
• rs4953617
• NM_000233.4:c.309-320G>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.309-320G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 152,044 control chromosomes in the GnomAD database, including 65,346 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 0.93 (65346 hom., cov: 29)
• Consequence: LHCGR NM_000233.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.666
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.309-320G>A		intron	N/A	NP_000224.2
	STON1-GTF2A1L	NM_001198593.2		c.3442-50210C>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.309-320G>A		intron	N/A	ENSP00000294954.6
	ENSG00000279956	ENST00000602369.3	TSL:5	n.234-320G>A		intron	N/A	ENSP00000473498.1
	STON1-GTF2A1L	ENST00000402114.6	TSL:2	c.3442-50210C>T		intron	N/A	ENSP00000385701.1

Frequencies

GnomAD3 genomes AF: 0.927 AC: 140778 AN: 151926 Hom.: 65293 Cov.: 29

Gnomad AFR AF: 0.958

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.945

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.976

Gnomad FIN AF: 0.903

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.937

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

GnomAD4 genome AF: 0.927 AC: 140890 AN: 152044 Hom.: 65346 Cov.: 29 AF XY: 0.928 AC XY: 68954 AN XY: 74302

African (AFR) AF: 0.958 AC: 39704 AN: 41458

American (AMR) AF: 0.945 AC: 14435 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2996 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5134 AN: 5140

South Asian (SAS) AF: 0.975 AC: 4684 AN: 4802

European-Finnish (FIN) AF: 0.903 AC: 9545 AN: 10576

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.902 AC: 61335 AN: 68000

Other (OTH) AF: 0.938 AC: 1982 AN: 2114

Alfa AF: 0.918 Hom.: 55223

Bravo AF: 0.932

Asia WGS AF: 0.986 AC: 3431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.14
DANN	Benign	0.58
PhyloP100		-0.67
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: rs4953617; hg19: chr2-48953209;