4-17859587-T-C

Variant names:

• chr4-17859587-T-C
• rs6854334
• NM_001394446.1:c.5603-13686A>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.5603-13686A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,050 control chromosomes in the GnomAD database, including 4,938 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 0.22 (4938 hom., cov: 32)
• Consequence: LCORL NM_001394446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 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.5603-13686A>G		intron	N/A	NP_001381375.1
	LCORL	NM_001365660.1		c.803+7412A>G		intron	N/A	NP_001352589.1
	LCORL	NM_153686.8		c.777-13686A>G		intron	N/A	NP_710153.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCORL	ENST00000635767.2	TSL:5 MANE Select	c.5603-13686A>G		intron	N/A	ENSP00000490600.1
	LCORL	ENST00000326877.8	TSL:1	c.777-13686A>G		intron	N/A	ENSP00000317566.3
	LCORL	ENST00000675605.1		c.1278+7412A>G		intron	N/A	ENSP00000501939.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34112 AN: 151932 Hom.: 4912 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.0909

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.225 AC: 34182 AN: 152050 Hom.: 4938 Cov.: 32 AF XY: 0.221 AC XY: 16437 AN XY: 74362

African (AFR) AF: 0.409 AC: 16929 AN: 41426

American (AMR) AF: 0.180 AC: 2746 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 940 AN: 3472

East Asian (EAS) AF: 0.137 AC: 712 AN: 5180

South Asian (SAS) AF: 0.273 AC: 1315 AN: 4820

European-Finnish (FIN) AF: 0.0909 AC: 963 AN: 10592

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9928 AN: 67954

Other (OTH) AF: 0.214 AC: 452 AN: 2116

Alfa AF: 0.170 Hom.: 5586

Bravo AF: 0.236

Asia WGS AF: 0.231 AC: 805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.60
PhyloP100		-0.13
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: rs6854334; hg19: chr4-17861210;