rs6817306

Positions:

• chr4-17866435-T-C

Variant summary

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

The NM_001394446.1(LCORL):​c.5602+6953A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,188 control chromosomes in the GnomAD database, including 3,243 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 0.19 (3243 hom., cov: 32)
• Consequence: LCORL NM_001394446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.503

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCORL	NM_001394446.1	c.5602+6953A>G		intron_variant		ENST00000635767.2	NP_001381375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCORL	ENST00000635767.2	c.5602+6953A>G		intron_variant		5	NM_001394446.1	ENSP00000490600

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29190 AN: 152070 Hom.: 3224 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.0868

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.192 AC: 29244 AN: 152188 Hom.: 3243 Cov.: 32 AF XY: 0.190 AC XY: 14138 AN XY: 74418

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.0868

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.191

Alfa AF: 0.163 Hom.: 1354

Bravo AF: 0.199

Asia WGS AF: 0.219 AC: 763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6817306; hg19: chr4-17868058;