4-17884186-C-T

Variant names:

• chr4-17884186-C-T
• rs763457238
• NM_001394446.1:c.776+1882G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001166139.2(LCORL):​c.1343G>A​(p.Gly448Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,397,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G448V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LCORL NM_001166139.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21826437).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166139.2. 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
	LCORL	NM_001394446.1	MANE Select	c.776+1882G>A		intron	N/A	NP_001381375.1	A0A1B0GVP4
	LCORL	NM_001166139.2		c.1343G>A	p.Gly448Glu	missense	Exon 7 of 7	NP_001159611.1	Q8N3X6-1
	LCORL	NM_001365658.1		c.863G>A	p.Gly288Glu	missense	Exon 8 of 8	NP_001352587.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCORL	ENST00000635767.2	TSL:5 MANE Select	c.776+1882G>A		intron	N/A	ENSP00000490600.1	A0A1B0GVP4
	LCORL	ENST00000326877.8	TSL:1	c.776+1882G>A		intron	N/A	ENSP00000317566.3	Q8N3X6-3
	LCORL	ENST00000382226.5	TSL:5	c.1343G>A	p.Gly448Glu	missense	Exon 7 of 7	ENSP00000371661.5	Q8N3X6-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1397782 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 689428

African (AFR) AF: 0.00 AC: 0 AN: 31438

American (AMR) AF: 0.00 AC: 0 AN: 35408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25016

East Asian (EAS) AF: 0.0000560 AC: 2 AN: 35728

South Asian (SAS) AF: 0.00 AC: 0 AN: 79082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078214

Other (OTH) AF: 0.00 AC: 0 AN: 57936

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0012	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.3
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.17
Sift	Benign	0.16	T
Sift4G	Benign	0.37	T
Vest4		0.46
MutPred		0.20		Gain of ubiquitination at K453 (P = 0.0329)
MVP		0.18
MPC		1.5
ClinPred		0.47	T
GERP RS		5.2
Varity_R		0.15
gMVP		0.28
Mutation Taster		=88/12	polymorphism

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: rs763457238; hg19: chr4-17885809;