rs2707450

Positions:

• chr4-17940937-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+20966G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,088 control chromosomes in the GnomAD database, including 40,569 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 0.73 (40569 hom., cov: 32)
• Consequence: LCORL NM_001394446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563

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 = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCORL	NM_001394446.1	c.430+20966G>A		intron_variant		ENST00000635767.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCORL	ENST00000635767.2	c.430+20966G>A		intron_variant		5	NM_001394446.1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110645 AN: 151970 Hom.: 40514 Cov.: 32

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.734

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

GnomAD4 genome AF: 0.728 AC: 110762 AN: 152088 Hom.: 40569 Cov.: 32 AF XY: 0.725 AC XY: 53880 AN XY: 74342

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.760

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.853

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.741

Gnomad4 OTH AF: 0.736

Alfa AF: 0.748 Hom.: 19275

Bravo AF: 0.722

Asia WGS AF: 0.707 AC: 2463 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	1.5
DANN	Benign	0.36

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: rs2707450; hg19: chr4-17942560;