4-17890777-T-G

Variant names:

• chr4-17890777-T-G
• rs13103931
• NM_001394446.1:c.683-4616A>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.683-4616A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,106 control chromosomes in the GnomAD database, including 1,316 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 (1316 hom., cov: 32)
• Consequence: LCORL NM_001394446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.228 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.683-4616A>C		intron	N/A	NP_001381375.1
	LCORL	NM_001166139.2		c.683-4616A>C		intron	N/A	NP_001159611.1
	LCORL	NM_001365658.1		c.203-4616A>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.683-4616A>C		intron	N/A	ENSP00000490600.1
	LCORL	ENST00000326877.8	TSL:1	c.683-4616A>C		intron	N/A	ENSP00000317566.3
	LCORL	ENST00000382226.5	TSL:5	c.683-4616A>C		intron	N/A	ENSP00000371661.5

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19079 AN: 151988 Hom.: 1314 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.0560

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.125 AC: 19089 AN: 152106 Hom.: 1316 Cov.: 32 AF XY: 0.125 AC XY: 9271 AN XY: 74358

African (AFR) AF: 0.103 AC: 4270 AN: 41534

American (AMR) AF: 0.138 AC: 2101 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 820 AN: 3468

East Asian (EAS) AF: 0.138 AC: 714 AN: 5178

South Asian (SAS) AF: 0.240 AC: 1155 AN: 4814

European-Finnish (FIN) AF: 0.0560 AC: 594 AN: 10608

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8884 AN: 67920

Other (OTH) AF: 0.148 AC: 312 AN: 2106

Alfa AF: 0.0934 Hom.: 242

Bravo AF: 0.130

Asia WGS AF: 0.192 AC: 667 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.56
PhyloP100		-0.15
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: rs13103931; hg19: chr4-17892400;