chr4-17883925-G-C

Variant names:

• chr4-17883925-G-C
• rs369527567
• NM_001394446.1:c.776+2143C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001166139.2(LCORL):​c.1604C>G​(p.Ala535Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LCORL NM_001166139.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.64
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28560597).

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+2143C>G		intron	N/A	NP_001381375.1	A0A1B0GVP4
	LCORL	NM_001166139.2		c.1604C>G	p.Ala535Gly	missense	Exon 7 of 7	NP_001159611.1	Q8N3X6-1
	LCORL	NM_001365658.1		c.1124C>G	p.Ala375Gly	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+2143C>G		intron	N/A	ENSP00000490600.1	A0A1B0GVP4
	LCORL	ENST00000326877.8	TSL:1	c.776+2143C>G		intron	N/A	ENSP00000317566.3	Q8N3X6-3
	LCORL	ENST00000382226.5	TSL:5	c.1604C>G	p.Ala535Gly	missense	Exon 7 of 7	ENSP00000371661.5	Q8N3X6-1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151810 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

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: 0.00000639 AC: 1 AN: 156610 AF XY: 0.0000121

Gnomad AFR exome AF: 0.00

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: 0.00

Gnomad OTH exome AF: 0.000228

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398808 Hom.: 0 Cov.: 34 AF XY: 0.00000290 AC XY: 2 AN XY: 689930

African (AFR) AF: 0.00 AC: 0 AN: 31548

American (AMR) AF: 0.0000560 AC: 2 AN: 35692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25148

East Asian (EAS) AF: 0.00 AC: 0 AN: 35732

South Asian (SAS) AF: 0.00 AC: 0 AN: 79208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078504

Other (OTH) AF: 0.00 AC: 0 AN: 57984

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151810 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74126

African (AFR) AF: 0.00 AC: 0 AN: 41378

American (AMR) AF: 0.0000658 AC: 1 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67874

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.69	N
PhyloP100		6.6
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.50
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.034	D
Vest4		0.27
MutPred		0.70		Loss of stability (P = 0.0442)
MVP		0.36
MPC		0.55
ClinPred		0.73	D
GERP RS		4.9
Varity_R		0.28
gMVP		0.59
Mutation Taster		=85/15	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: rs369527567; hg19: chr4-17885548;