Genetic Variant LCORL:c.777-1649A>G (chr4-17879862-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001394446.1(LCORL):c.777-1649A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 151,006 control chromosomes in the GnomAD database, including 1,778 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.10 ( 1778 hom., cov: 32)

Consequence

LCORL
NM_001394446.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.57

Publications

2 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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new If you want to explore the variant's impact on the transcript NM_001394446.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394446.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LCORL	NM_001394446.1	MANE Select	c.777-1649A>G	intron	N/A	NP_001381375.1	A0A1B0GVP4
LCORL	NM_001365660.1		c.776+6206A>G	intron	N/A	NP_001352589.1	A0A6Q8PHE0
LCORL	NM_153686.8		c.776+6206A>G	intron	N/A	NP_710153.2	B4DSW0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LCORL	ENST00000635767.2	TSL:5 MANE Select	c.777-1649A>G	intron	N/A	ENSP00000490600.1	A0A1B0GVP4
LCORL	ENST00000326877.8	TSL:1	c.776+6206A>G	intron	N/A	ENSP00000317566.3	Q8N3X6-3
LCORL	ENST00000675605.1		c.1251+4413A>G	intron	N/A	ENSP00000501939.1	A0A6Q8PFT7

Frequencies

GnomAD3 genomes

AF:

0.100

AC:

15155

AN:

150888

Hom.:

1763

Cov.:

show subpopulations

Gnomad AFR

AF:

0.287

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0489

Gnomad ASJ

AF:

0.0441

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.0330

Gnomad FIN

AF:

0.0356

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0262

Gnomad OTH

AF:

0.0672

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.101

AC:

15206

AN:

151006

Hom.:

1778

Cov.:

AF XY:

0.0976

AC XY:

7203

AN XY:

73786

show subpopulations

African (AFR)

AF:

0.287

AC:

11871

AN:

41346

American (AMR)

AF:

0.0489

AC:

739

AN:

15124

Ashkenazi Jewish (ASJ)

AF:

0.0441

AC:

152

AN:

3448

East Asian (EAS)

AF:

0.000388

AC:

AN:

5154

South Asian (SAS)

AF:

0.0320

AC:

154

AN:

4818

European-Finnish (FIN)

AF:

0.0356

AC:

377

AN:

10604

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0262

AC:

1759

AN:

67216

Other (OTH)

AF:

0.0665

AC:

139

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

590

1180

1771

2361

2951

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0959

Hom.:

244

Bravo

AF:

0.107

Asia WGS

AF:

0.0320

AC:

110

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.091

(source)

DANN

Benign

0.29

PhyloP100

-3.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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