4-17884711-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394446.1(LCORL):c.776+1357C>G variant causes a intron change. The variant allele was found at a frequency of 0.00000517 in 1,354,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000052 (0 hom.)
• Consequence: LCORL NM_001394446.1 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.76

Genes affected

LCORL (HGNC:30776): (ligand dependent nuclear receptor corepressor like) This gene encodes a transcription factor that appears to function in spermatogenesis. Polymorphisms in this gene are associated with measures of skeletal frame size and adult height. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15891108).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCORL	NM_001394446.1	c.776+1357C>G		intron_variant		ENST00000635767.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCORL	ENST00000635767.2	c.776+1357C>G		intron_variant		5	NM_001394446.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000878 AC: 1 AN: 113870 Hom.: 0 AF XY: 0.0000170 AC XY: 1 AN XY: 58954

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000217

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000517 AC: 7 AN: 1354518 Hom.: 0 Cov.: 33 AF XY: 0.00000300 AC XY: 2 AN XY: 666038

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000659

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 09, 2022

The c.818C>G (p.A273G) alteration is located in exon 7 (coding exon 7) of the LCORL gene. This alteration results from a C to G substitution at nucleotide position 818, causing the alanine (A) at amino acid position 273 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	0.0056	T
BayesDel_noAF	Benign	-0.19
Cadd	Benign	23
Dann	Uncertain	0.98
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.66	T
MutationTaster	Benign	0.98	D;D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.47	N;N
REVEL	Benign	0.13
Sift	Benign	0.21	T;D
Sift4G	Benign	0.45	T;T
Vest4		0.28
MutPred		0.15		.;Gain of glycosylation at Y268 (P = 0.0173);
MVP		0.34
MPC		0.93
ClinPred		0.32	T
GERP RS		5.1
Varity_R		0.17
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs1288930412; hg19: chr4-17886334;