rs11246178

Variant names:

• chr11-540584-G-A
• rs11246178
• NM_198075.4:c.-11-90G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-540584-G-A
• chr11-540584-G-C
• chr11-540584-G-T

Variant summary

Our verdict is Benign. The variant received -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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.69
• Publications: 1 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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198075.4. 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
	LRRC56	NM_198075.4	MANE Select	c.-11-90G>A		intron	N/A	NP_932341.1	Q8IYG6
	LRRC56	NM_001441283.1		c.-14-87G>A		intron	N/A	NP_001428212.1
	LRRC56	NM_001441284.1		c.-14-87G>A		intron	N/A	NP_001428213.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC56	ENST00000270115.8	TSL:1 MANE Select	c.-11-90G>A		intron	N/A	ENSP00000270115.7	Q8IYG6
	LRRC56	ENST00000886180.1		c.-14-87G>A		intron	N/A	ENSP00000556239.1
	LRRC56	ENST00000886182.1		c.-11-90G>A		intron	N/A	ENSP00000556241.1

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

African (AFR) AF: 0.116 AC: 2591 AN: 22264

American (AMR) AF: 0.0640 AC: 1603 AN: 25060

Ashkenazi Jewish (ASJ) AF: 0.0841 AC: 1699 AN: 20214

East Asian (EAS) AF: 0.0996 AC: 3274 AN: 32866

South Asian (SAS) AF: 0.178 AC: 11676 AN: 65424

European-Finnish (FIN) AF: 0.134 AC: 5053 AN: 37804

Middle Eastern (MID) AF: 0.108 AC: 363 AN: 3348

European-Non Finnish (NFE) AF: 0.123 AC: 88109 AN: 716124

Other (OTH) AF: 0.114 AC: 4955 AN: 43396

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

African (AFR) AF: 0.114 AC: 4709 AN: 41470

American (AMR) AF: 0.0840 AC: 1283 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0839 AC: 291 AN: 3468

East Asian (EAS) AF: 0.124 AC: 642 AN: 5158

South Asian (SAS) AF: 0.183 AC: 878 AN: 4810

European-Finnish (FIN) AF: 0.116 AC: 1228 AN: 10580

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.121 AC: 8238 AN: 67910

Other (OTH) AF: 0.107 AC: 225 AN: 2102

Alfa AF: 0.0453 Hom.: 43

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.85
DANN	Benign	0.84
PhyloP100		-2.7
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: rs11246178; hg19: chr11-540584;