4-17889337-A-G

Position:

• chr4-17889337-A-G

Variant summary

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

The NM_001394446.1(LCORL):​c.683-3176T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,064 control chromosomes in the GnomAD database, including 1,308 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 0.12 (1308 hom., cov: 32)
• Consequence: LCORL NM_001394446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

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]

LCORL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCORL	NM_001394446.1	c.683-3176T>C		intron_variant		ENST00000635767.2	NP_001381375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCORL	ENST00000635767.2	c.683-3176T>C		intron_variant		5	NM_001394446.1	ENSP00000490600.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18908 AN: 151946 Hom.: 1304 Cov.: 32

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.0571

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.124 AC: 18919 AN: 152064 Hom.: 1308 Cov.: 32 AF XY: 0.124 AC XY: 9198 AN XY: 74336

Gnomad4 AFR AF: 0.0951

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.0571

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.152

Alfa AF: 0.0351 Hom.: 19

Bravo AF: 0.128

Asia WGS AF: 0.192 AC: 669 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.73

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: rs13141926; hg19: chr4-17890960;