NM_001394446.1:c.5603-7244A>G

Variant names:

• chr4-17853145-T-C
• rs16895895
• NM_001394446.1:c.5603-7244A>G

Variant summary

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

The NM_001394446.1(LCORL):​c.5603-7244A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 147,000 control chromosomes in the GnomAD database, including 1,127 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 (1127 hom., cov: 30)
• Consequence: LCORL NM_001394446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.730
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.239 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.5603-7244A>G		intron	N/A	NP_001381375.1
	LCORL	NM_001365660.1		c.804-7244A>G		intron	N/A	NP_001352589.1
	LCORL	NM_153686.8		c.777-7244A>G		intron	N/A	NP_710153.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCORL	ENST00000635767.2	TSL:5 MANE Select	c.5603-7244A>G		intron	N/A	ENSP00000490600.1
	LCORL	ENST00000326877.8	TSL:1	c.777-7244A>G		intron	N/A	ENSP00000317566.3
	LCORL	ENST00000675605.1		c.1279-7244A>G		intron	N/A	ENSP00000501939.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 17477 AN: 146878 Hom.: 1123 Cov.: 30

Gnomad AFR AF: 0.0934

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.0603

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.119 AC: 17490 AN: 147000 Hom.: 1127 Cov.: 30 AF XY: 0.119 AC XY: 8505 AN XY: 71416

African (AFR) AF: 0.0933 AC: 3723 AN: 39910

American (AMR) AF: 0.134 AC: 1942 AN: 14472

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 792 AN: 3436

East Asian (EAS) AF: 0.144 AC: 705 AN: 4884

South Asian (SAS) AF: 0.251 AC: 1158 AN: 4608

European-Finnish (FIN) AF: 0.0603 AC: 576 AN: 9560

Middle Eastern (MID) AF: 0.120 AC: 33 AN: 276

European-Non Finnish (NFE) AF: 0.121 AC: 8127 AN: 66916

Other (OTH) AF: 0.139 AC: 284 AN: 2036

Alfa AF: 0.126 Hom.: 2612

Bravo AF: 0.118

Asia WGS AF: 0.190 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.76
DANN	Benign	0.43
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs16895895; hg19: chr4-17854768;