4-17944809-T-C

Variant names:

• chr4-17944809-T-C
• rs2724475
• NM_001394446.1:c.430+17094A>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.430+17094A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 152,000 control chromosomes in the GnomAD database, including 38,789 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 0.71 (38789 hom., cov: 31)
• Consequence: LCORL NM_001394446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197
• Publications: 16 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=-1.05).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.833 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.430+17094A>G		intron	N/A	NP_001381375.1
	LCORL	NM_001166139.2		c.430+17094A>G		intron	N/A	NP_001159611.1
	LCORL	NM_001365658.1		c.-51+15456A>G		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.430+17094A>G		intron	N/A	ENSP00000490600.1
	LCORL	ENST00000326877.8	TSL:1	c.430+17094A>G		intron	N/A	ENSP00000317566.3
	LCORL	ENST00000382226.5	TSL:5	c.430+17094A>G		intron	N/A	ENSP00000371661.5

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108115 AN: 151882 Hom.: 38743 Cov.: 31

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.712 AC: 108221 AN: 152000 Hom.: 38789 Cov.: 31 AF XY: 0.709 AC XY: 52649 AN XY: 74304

African (AFR) AF: 0.688 AC: 28505 AN: 41446

American (AMR) AF: 0.670 AC: 10224 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 2630 AN: 3468

East Asian (EAS) AF: 0.542 AC: 2801 AN: 5166

South Asian (SAS) AF: 0.855 AC: 4116 AN: 4816

European-Finnish (FIN) AF: 0.681 AC: 7203 AN: 10570

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50311 AN: 67956

Other (OTH) AF: 0.710 AC: 1496 AN: 2108

Alfa AF: 0.724 Hom.: 58376

Bravo AF: 0.703

Asia WGS AF: 0.706 AC: 2458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.52
DANN	Benign	0.28
PhyloP100		-0.20
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: rs2724475; hg19: chr4-17946432;