dbSNP rs16895971: LCORL:c.776+2705A>G (chr4-17883363-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001394446.1(LCORL):c.776+2705A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,020,714 control chromosomes in the GnomAD database, including 10,668 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 0.13 ( 1592 hom., cov: 32)

Exomes 𝑓: 0.14 ( 9076 hom. )

Consequence

LCORL
NM_001394446.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.84

Publications

13 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:

Genome browser will be placed here

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=-0.49).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.279 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
LCORL	NM_001394446.1	MANE Select	c.776+2705A>G	intron	N/A	NP_001381375.1
LCORL	NR_158567.1		n.2116A>G	non_coding_transcript_exon	Exon 5 of 5
LCORL	NM_001166139.2		c.*357A>G	3_prime_UTR	Exon 7 of 7	NP_001159611.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LCORL	ENST00000635767.2	TSL:5 MANE Select	c.776+2705A>G	intron	N/A	ENSP00000490600.1
LCORL	ENST00000326877.8	TSL:1	c.776+2705A>G	intron	N/A	ENSP00000317566.3
LCORL	ENST00000676061.1		n.*1700A>G	non_coding_transcript_exon	Exon 8 of 8	ENSP00000501720.1

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20381

AN:

151632

Hom.:

1588

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.219

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.238

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.0612

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.160

GnomAD4 exome

AF:

0.140

AC:

122088

AN:

868964

Hom.:

9076

Cov.:

AF XY:

0.141

AC XY:

56811

AN XY:

403310

show subpopulations

African (AFR)

AF:

0.104

AC:

1785

AN:

17124

American (AMR)

AF:

0.125

AC:

407

AN:

3264

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

1529

AN:

6404

East Asian (EAS)

AF:

0.255

AC:

1524

AN:

5966

South Asian (SAS)

AF:

0.277

AC:

4804

AN:

17366

European-Finnish (FIN)

AF:

0.0622

AC:

117

AN:

1882

Middle Eastern (MID)

AF:

0.178

AC:

315

AN:

1774

European-Non Finnish (NFE)

AF:

0.136

AC:

106786

AN:

785502

Other (OTH)

AF:

0.162

AC:

4821

AN:

29682

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

4820

9639

14459

19278

24098

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5320

10640

15960

21280

26600

<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

AF:

0.134

AC:

20402

AN:

151750

Hom.:

1592

Cov.:

AF XY:

0.135

AC XY:

10012

AN XY:

74158

show subpopulations

African (AFR)

AF:

0.104

AC:

4309

AN:

41432

American (AMR)

AF:

0.141

AC:

2146

AN:

15178

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

821

AN:

3456

East Asian (EAS)

AF:

0.275

AC:

1419

AN:

5154

South Asian (SAS)

AF:

0.292

AC:

1407

AN:

4816

European-Finnish (FIN)

AF:

0.0612

AC:

650

AN:

10614

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.134

AC:

9061

AN:

67786

Other (OTH)

AF:

0.165

AC:

347

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

892

1784

2676

3568

4460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

244

488

732

976

1220

<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:

0.138

Hom.:

1249

Bravo

AF:

0.139

Asia WGS

AF:

0.287

AC:

1000

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

1.8

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over