4-17993689-T-C

Variant names:

• chr4-17993689-T-C
• rs16896215
• NM_001394446.1:c.155-20804A>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.155-20804A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,112 control chromosomes in the GnomAD database, including 5,887 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 0.24 (5887 hom., cov: 32)
• Consequence: LCORL NM_001394446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.636
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCORL	NM_001394446.1	MANE Select	c.155-20804A>G		intron	N/A	NP_001381375.1
	LCORL	NM_001166139.2		c.155-20804A>G		intron	N/A	NP_001159611.1
	LCORL	NM_001365658.1		c.-373-20804A>G		intron	N/A	NP_001352587.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCORL	ENST00000635767.2	TSL:5 MANE Select	c.155-20804A>G		intron	N/A	ENSP00000490600.1
	LCORL	ENST00000326877.8	TSL:1	c.155-20804A>G		intron	N/A	ENSP00000317566.3
	LCORL	ENST00000382226.5	TSL:5	c.155-20804A>G		intron	N/A	ENSP00000371661.5

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36994 AN: 151994 Hom.: 5855 Cov.: 32

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.0910

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.244 AC: 37069 AN: 152112 Hom.: 5887 Cov.: 32 AF XY: 0.239 AC XY: 17779 AN XY: 74362

African (AFR) AF: 0.447 AC: 18545 AN: 41470

American (AMR) AF: 0.197 AC: 3004 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 977 AN: 3468

East Asian (EAS) AF: 0.137 AC: 708 AN: 5172

South Asian (SAS) AF: 0.277 AC: 1332 AN: 4812

European-Finnish (FIN) AF: 0.0910 AC: 964 AN: 10590

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10751 AN: 68002

Other (OTH) AF: 0.237 AC: 501 AN: 2114

Alfa AF: 0.256 Hom.: 2526

Bravo AF: 0.257

Asia WGS AF: 0.232 AC: 808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.65
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism (auto)

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: rs16896215; hg19: chr4-17995312;