rs10489042

Variant names:

• chr4-17879862-T-C
• rs10489042
• NM_001394446.1:c.777-1649A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.57
• Publications: 2 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: 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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.: 32

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.: 32 AF XY: 0.0976 AC XY: 7203 AN XY: 73786

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: 2 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: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0262 AC: 1759 AN: 67216

Other (OTH) AF: 0.0665 AC: 139 AN: 2090

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
DANN	Benign	0.29
PhyloP100		-3.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10489042; hg19: chr4-17881485;