Genetic Variant LCORL:c.776+1960G>T (chr4-17884108-C-A) – 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.1421G>T(p.Ser474Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. S474N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

LCORL
NM_001166139.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.49

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=0.17633057).

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+1960G>T		intron	N/A	NP_001381375.1	A0A1B0GVP4
LCORL	NM_001166139.2		c.1421G>T	p.Ser474Ile	missense	Exon 7 of 7	NP_001159611.1	Q8N3X6-1
LCORL	NM_001365658.1		c.941G>T	p.Ser314Ile	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+1960G>T		intron	N/A	ENSP00000490600.1	A0A1B0GVP4
LCORL	ENST00000326877.8	TSL:1	c.776+1960G>T		intron	N/A	ENSP00000317566.3	Q8N3X6-3
LCORL	ENST00000382226.5	TSL:5	c.1421G>T	p.Ser474Ile	missense	Exon 7 of 7	ENSP00000371661.5	Q8N3X6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1398764

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689894

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31548

American (AMR)

AF:

0.00

AC:

AN:

35696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25126

East Asian (EAS)

AF:

0.00

AC:

AN:

35730

South Asian (SAS)

AF:

0.00

AC:

AN:

79212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49286

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078494

Other (OTH)

AF:

0.00

AC:

AN:

57978

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

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.0030

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0053

Eigen

Benign

0.017

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.84

M_CAP

Benign

0.0081

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.34

PhyloP100

1.5

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.49

REVEL

Benign

0.12

Sift

Uncertain

0.021

Sift4G

Uncertain

0.023

Vest4

0.35

MutPred

0.36

Loss of disorder (P = 0.0041)

MVP

0.23

MPC

0.76

ClinPred

0.26

GERP RS

3.1

Varity_R

0.11

gMVP

0.76

Mutation Taster

=96/4

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over