chr11-511805-C-T

Variant names:

• chr11-511805-C-T
• rs12420868
• XM_047426336.1:c.-679+4539C>T

Variant summary

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

The XM_047426336.1(LRRC56):​c.-679+4539C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,166 control chromosomes in the GnomAD database, including 3,855 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 0.22 (3855 hom., cov: 32)
• Consequence: LRRC56 XM_047426336.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.766
• Publications: 24 publications found

Genes affected

LRRC56 (HGNC:25430): (leucine rich repeat containing 56) Predicted to be involved in cell projection organization. Predicted to be located in cilium. Implicated in primary ciliary dyskinesia 39. [provided by Alliance of Genome Resources, Apr 2022]

LRRC56 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 39

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC56	XM_047426336.1	c.-679+4539C>T		intron_variant	Intron 1 of 14		XP_047282292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33232 AN: 152048 Hom.: 3848 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.219 AC: 33253 AN: 152166 Hom.: 3855 Cov.: 32 AF XY: 0.218 AC XY: 16235 AN XY: 74408

African (AFR) AF: 0.299 AC: 12387 AN: 41484

American (AMR) AF: 0.169 AC: 2584 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 797 AN: 3466

East Asian (EAS) AF: 0.184 AC: 953 AN: 5188

South Asian (SAS) AF: 0.202 AC: 976 AN: 4824

European-Finnish (FIN) AF: 0.186 AC: 1978 AN: 10606

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12811 AN: 67994

Other (OTH) AF: 0.223 AC: 471 AN: 2116

Alfa AF: 0.199 Hom.: 8082

Bravo AF: 0.218

Asia WGS AF: 0.214 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.77
PhyloP100		0.77

Splicing

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

Other links and lift over

dbSNP: rs12420868; hg19: chr11-511805;