4-17950585-C-T

Position:

• chr4-17950585-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394446.1(LCORL):​c.430+11318G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 151,862 control chromosomes in the GnomAD database, including 6,197 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 0.25 (6197 hom., cov: 32)
• Consequence: LCORL NM_001394446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCORL	NM_001394446.1	c.430+11318G>A		intron_variant		ENST00000635767.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCORL	ENST00000635767.2	c.430+11318G>A		intron_variant		5	NM_001394446.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37743 AN: 151744 Hom.: 6165 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.0922

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.249 AC: 37820 AN: 151862 Hom.: 6197 Cov.: 32 AF XY: 0.245 AC XY: 18152 AN XY: 74194

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.0922

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.243

Alfa AF: 0.165 Hom.: 964

Bravo AF: 0.264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.37

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

LitVar

Other links and lift over

dbSNP: rs6845078; hg19: chr4-17952208;