chr11-540710-G-T

Variant names:

• chr11-540710-G-T
• rs778566046
• NM_198075.4:c.26G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198075.4(LRRC56):​c.26G>T​(p.Arg9Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R9H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LRRC56 NM_198075.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.033387065).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC56	NM_198075.4	c.26G>T	p.Arg9Leu	missense_variant	Exon 4 of 14	ENST00000270115.8	NP_932341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC56	ENST00000270115.8	c.26G>T	p.Arg9Leu	missense_variant	Exon 4 of 14	1	NM_198075.4	ENSP00000270115.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000806 AC: 2 AN: 248242 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460388 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726420

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111832

Other (OTH) AF: 0.00 AC: 0 AN: 60348

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.022
DANN	Benign	0.80
DEOGEN2	Benign	0.0014	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		-1.5
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.011
Sift	Benign	0.29	T
Sift4G	Benign	0.47	T
Polyphen		0.049	B
Vest4		0.10
MutPred		0.35		Loss of solvent accessibility (P = 0.0217);
MVP		0.055
ClinPred		0.077	T
GERP RS		-9.8
Varity_R		0.045
gMVP		0.44
Mutation Taster		=96/4	polymorphism

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

dbSNP: rs778566046; hg19: chr11-540710;