chr4-17990056-T-C

Position:

• chr4-17990056-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.155-17171A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 151,512 control chromosomes in the GnomAD database, including 1,350 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 (1350 hom., cov: 31)
• Consequence: LCORL NM_001394446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.709

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCORL	NM_001394446.1	c.155-17171A>G		intron_variant		ENST00000635767.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCORL	ENST00000635767.2	c.155-17171A>G		intron_variant		5	NM_001394446.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19144 AN: 151428 Hom.: 1346 Cov.: 31

Gnomad AFR AF: 0.0913

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.0717

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.126 AC: 19149 AN: 151512 Hom.: 1350 Cov.: 31 AF XY: 0.126 AC XY: 9309 AN XY: 74008

Gnomad4 AFR AF: 0.0912

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.0717

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.147

Alfa AF: 0.123 Hom.: 192

Bravo AF: 0.129

Asia WGS AF: 0.196 AC: 683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.5
DANN	Benign	0.63

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: rs13151620; hg19: chr4-17991679;