2-48687643-A-AT

Position:

• chr2-48687643-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000233.4(LHCGR):​c.*53_*54insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,437,204 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (1 hom.)
• Consequence: LHCGR NM_000233.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.441

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 -10 ACMG points.

• BP6: Variant 2-48687643-A-AT is Benign according to our data. Variant chr2-48687643-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 1189231.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00339 (514/151684) while in subpopulation AFR AF= 0.0111 (460/41376). AF 95% confidence interval is 0.0103. There are 6 homozygotes in gnomad4. There are 239 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LHCGR	NM_000233.4	c.*53_*54insA		3_prime_UTR_variant	11/11	ENST00000294954.12
STON1-GTF2A1L	NM_001198593.2	c.3441+15972dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHCGR	ENST00000294954.12	c.*53_*54insA		3_prime_UTR_variant	11/11	1	NM_000233.4	A2

Frequencies

GnomAD3 genomes AF: 0.00338 AC: 513 AN: 151570 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00158

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.000339

Gnomad OTH AF: 0.00192

GnomAD4 exome AF: 0.00105 AC: 1349 AN: 1285520 Hom.: 1 Cov.: 19 AF XY: 0.000967 AC XY: 627 AN XY: 648184

Gnomad4 AFR exome AF: 0.0116

Gnomad4 AMR exome AF: 0.000873

Gnomad4 ASJ exome AF: 0.000161

Gnomad4 EAS exome AF: 0.000207

Gnomad4 SAS exome AF: 0.000343

Gnomad4 FIN exome AF: 0.000134

Gnomad4 NFE exome AF: 0.000888

Gnomad4 OTH exome AF: 0.00129

GnomAD4 genome AF: 0.00339 AC: 514 AN: 151684 Hom.: 6 Cov.: 32 AF XY: 0.00322 AC XY: 239 AN XY: 74136

Gnomad4 AFR AF: 0.0111

Gnomad4 AMR AF: 0.00158

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000339

Gnomad4 OTH AF: 0.00190

Bravo AF: 0.00407

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 18, 2020

- -

Computational scores

Source: dbNSFP v4.3

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: rs200887026; hg19: chr2-48914782;