4-17852432-T-G

Variant names:

• chr4-17852432-T-G
• rs6842303
• NM_001394446.1:c.5603-6531A>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.5603-6531A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 151,964 control chromosomes in the GnomAD database, including 41,068 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 0.73 (41068 hom., cov: 32)
• Consequence: LCORL NM_001394446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• Publications: 20 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.832 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCORL	NM_001394446.1	MANE Select	c.5603-6531A>C		intron	N/A	NP_001381375.1	A0A1B0GVP4
	LCORL	NM_001365660.1		c.804-6531A>C		intron	N/A	NP_001352589.1	A0A6Q8PHE0
	LCORL	NM_153686.8		c.777-6531A>C		intron	N/A	NP_710153.2	B4DSW0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCORL	ENST00000635767.2	TSL:5 MANE Select	c.5603-6531A>C		intron	N/A	ENSP00000490600.1	A0A1B0GVP4
	LCORL	ENST00000326877.8	TSL:1	c.777-6531A>C		intron	N/A	ENSP00000317566.3	Q8N3X6-3
	LCORL	ENST00000675605.1		c.1279-6531A>C		intron	N/A	ENSP00000501939.1	A0A6Q8PFT7

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111267 AN: 151848 Hom.: 41020 Cov.: 32

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.745

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

GnomAD4 genome AF: 0.733 AC: 111375 AN: 151964 Hom.: 41068 Cov.: 32 AF XY: 0.731 AC XY: 54269 AN XY: 74278

African (AFR) AF: 0.756 AC: 31346 AN: 41458

American (AMR) AF: 0.676 AC: 10309 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2778 AN: 3470

East Asian (EAS) AF: 0.541 AC: 2792 AN: 5162

South Asian (SAS) AF: 0.854 AC: 4119 AN: 4822

European-Finnish (FIN) AF: 0.720 AC: 7575 AN: 10528

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.735 AC: 49930 AN: 67950

Other (OTH) AF: 0.747 AC: 1577 AN: 2112

Alfa AF: 0.737 Hom.: 71682

Bravo AF: 0.725

Asia WGS AF: 0.712 AC: 2480 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.9
DANN	Benign	0.25
PhyloP100		-0.13
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: rs6842303; hg19: chr4-17854055;