chr11-540584-G-A

Position:

• chr11-540584-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198075.4(LRRC56):​c.-11-90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,118,480 control chromosomes in the GnomAD database, including 8,798 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1095 hom., cov: 31)
  • Exomes 𝑓: 0.12 (7703 hom.)
• Consequence: LRRC56 NM_198075.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.69

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-540584-G-A is Benign according to our data. Variant chr11-540584-G-A is described in ClinVar as [Benign]. Clinvar id is 1249779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC56	NM_198075.4	c.-11-90G>A		intron_variant		ENST00000270115.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC56	ENST00000270115.8	c.-11-90G>A		intron_variant		1	NM_198075.4	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17710 AN: 151864 Hom.: 1091 Cov.: 31

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.0843

Gnomad ASJ AF: 0.0839

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.123 AC: 119323 AN: 966500 Hom.: 7703 AF XY: 0.125 AC XY: 61082 AN XY: 486910

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.0640

Gnomad4 ASJ exome AF: 0.0841

Gnomad4 EAS exome AF: 0.0996

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.123

Gnomad4 OTH exome AF: 0.114

GnomAD4 genome AF: 0.117 AC: 17724 AN: 151980 Hom.: 1095 Cov.: 31 AF XY: 0.118 AC XY: 8781 AN XY: 74282

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0840

Gnomad4 ASJ AF: 0.0839

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0425 Hom.: 36

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.85
DANN	Benign	0.84

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

LitVar

Other links and lift over

dbSNP: rs11246178; hg19: chr11-540584;