rs16895971

chr4-17883363-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.776+2705A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,020,714 control chromosomes in the GnomAD database, including 10,668 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 0.13 (1592 hom., cov: 32)
  • Exomes 𝑓: 0.14 (9076 hom.)
• Consequence: LCORL NM_001394446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

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=-0.49).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCORL	NM_001394446.1	c.776+2705A>G		intron_variant		ENST00000635767.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCORL	ENST00000635767.2	c.776+2705A>G		intron_variant		5	NM_001394446.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20381 AN: 151632 Hom.: 1588 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.0612

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.140 AC: 122088 AN: 868964 Hom.: 9076 Cov.: 30 AF XY: 0.141 AC XY: 56811 AN XY: 403310

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.239

Gnomad4 EAS exome AF: 0.255

Gnomad4 SAS exome AF: 0.277

Gnomad4 FIN exome AF: 0.0622

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.134 AC: 20402 AN: 151750 Hom.: 1592 Cov.: 32 AF XY: 0.135 AC XY: 10012 AN XY: 74158

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.0612

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.165

Alfa AF: 0.136 Hom.: 504

Bravo AF: 0.139

Asia WGS AF: 0.287 AC: 1000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	18
Dann	Benign	0.84

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: rs16895971; hg19: chr4-17884986;