Genetic Variant LCORL:c.776+2143C>A (chr4-17883925-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001166139.2(LCORL):c.1604C>A(p.Ala535Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000193 in 1,550,618 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. A535G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LCORL
NM_001166139.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.64

Publications

0 publications found

Variant links:

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]

LCORL links:

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ACMG classification

Classification was made for transcript

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=0.14176252).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LCORL	NM_001394446.1	MANE Select	c.776+2143C>A		intron	N/A	NP_001381375.1	A0A1B0GVP4
LCORL	NM_001166139.2		c.1604C>A	p.Ala535Glu	missense	Exon 7 of 7	NP_001159611.1	Q8N3X6-1
LCORL	NM_001365658.1		c.1124C>A	p.Ala375Glu	missense	Exon 8 of 8	NP_001352587.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LCORL	ENST00000635767.2	TSL:5 MANE Select	c.776+2143C>A		intron	N/A	ENSP00000490600.1	A0A1B0GVP4
LCORL	ENST00000326877.8	TSL:1	c.776+2143C>A		intron	N/A	ENSP00000317566.3	Q8N3X6-3
LCORL	ENST00000382226.5	TSL:5	c.1604C>A	p.Ala535Glu	missense	Exon 7 of 7	ENSP00000371661.5	Q8N3X6-1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151810

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000128

AC:

AN:

156610

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000165

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1398808

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689930

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31548

American (AMR)

AF:

0.00

AC:

AN:

35692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25148

East Asian (EAS)

AF:

0.00

AC:

AN:

35732

South Asian (SAS)

AF:

0.00

AC:

AN:

79208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1078504

Other (OTH)

AF:

0.00

AC:

AN:

57984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151810

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74126

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41378

American (AMR)

AF:

0.00

AC:

AN:

15196

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67874

Other (OTH)

AF:

0.00

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000398

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0056

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.79

M_CAP

Benign

0.0093

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.89

MutationAssessor

Benign

-0.75

PhyloP100

6.6

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.010

REVEL

Benign

0.17

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.017

Vest4

0.34

MVP

0.23

MPC

0.63

ClinPred

0.23

GERP RS

4.9

Varity_R

0.35

gMVP

0.71

Mutation Taster

=88/12

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over