rs2320299

Positions:

• chr4-17970749-G-A

Variant summary

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

The NM_001394446.1(LCORL):​c.220+2071C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,046 control chromosomes in the GnomAD database, including 36,260 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 0.69 (36260 hom., cov: 32)
• Consequence: LCORL NM_001394446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCORL	NM_001394446.1	c.220+2071C>T		intron_variant		ENST00000635767.2	NP_001381375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCORL	ENST00000635767.2	c.220+2071C>T		intron_variant		5	NM_001394446.1	ENSP00000490600

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104256 AN: 151928 Hom.: 36228 Cov.: 32

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.686 AC: 104341 AN: 152046 Hom.: 36260 Cov.: 32 AF XY: 0.681 AC XY: 50629 AN XY: 74322

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.753

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.800

Gnomad4 FIN AF: 0.677

Gnomad4 NFE AF: 0.737

Gnomad4 OTH AF: 0.683

Alfa AF: 0.718 Hom.: 49454

Bravo AF: 0.675

Asia WGS AF: 0.604 AC: 2102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.17

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: rs2320299; hg19: chr4-17972372;