NM_001394446.1:c.155-13633T>C

Variant names:

• chr4-17986518-A-G
• rs7668933
• NM_001394446.1:c.155-13633T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394446.1(LCORL):​c.155-13633T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,002 control chromosomes in the GnomAD database, including 6,049 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 0.25 (6049 hom., cov: 32)
• Consequence: LCORL NM_001394446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394446.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCORL	NM_001394446.1	MANE Select	c.155-13633T>C		intron	N/A	NP_001381375.1
	LCORL	NM_001166139.2		c.155-13633T>C		intron	N/A	NP_001159611.1
	LCORL	NM_001365658.1		c.-373-13633T>C		intron	N/A	NP_001352587.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCORL	ENST00000635767.2	TSL:5 MANE Select	c.155-13633T>C		intron	N/A	ENSP00000490600.1
	LCORL	ENST00000326877.8	TSL:1	c.155-13633T>C		intron	N/A	ENSP00000317566.3
	LCORL	ENST00000382226.5	TSL:5	c.155-13633T>C		intron	N/A	ENSP00000371661.5

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37379 AN: 151884 Hom.: 6016 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.0912

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.246 AC: 37458 AN: 152002 Hom.: 6049 Cov.: 32 AF XY: 0.242 AC XY: 18011 AN XY: 74318

African (AFR) AF: 0.457 AC: 18921 AN: 41406

American (AMR) AF: 0.198 AC: 3034 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 978 AN: 3472

East Asian (EAS) AF: 0.137 AC: 711 AN: 5178

South Asian (SAS) AF: 0.280 AC: 1351 AN: 4818

European-Finnish (FIN) AF: 0.0912 AC: 965 AN: 10582

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10712 AN: 67942

Other (OTH) AF: 0.238 AC: 503 AN: 2114

Alfa AF: 0.205 Hom.: 684

Bravo AF: 0.260

Asia WGS AF: 0.242 AC: 845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.2
DANN	Benign	0.63
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7668933; hg19: chr4-17988141;