11-540604-A-C

Position:

• chr11-540604-A-C

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.-11-70A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,375,156 control chromosomes in the GnomAD database, including 10,342 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.098 (895 hom., cov: 32)
  • Exomes 𝑓: 0.12 (9447 hom.)
• Consequence: LRRC56 NM_198075.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.25

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=-0.86).
• BP6: Variant 11-540604-A-C is Benign according to our data. Variant chr11-540604-A-C is described in ClinVar as [Benign]. Clinvar id is 1266903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC56	NM_198075.4	c.-11-70A>C		intron_variant		ENST00000270115.8	NP_932341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC56	ENST00000270115.8	c.-11-70A>C		intron_variant		1	NM_198075.4	ENSP00000270115.7

Frequencies

GnomAD3 genomes AF: 0.0984 AC: 14954 AN: 152036 Hom.: 892 Cov.: 32

Gnomad AFR AF: 0.0500

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.0770

Gnomad ASJ AF: 0.0842

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0844

GnomAD4 exome AF: 0.122 AC: 148954 AN: 1223002 Hom.: 9447 AF XY: 0.124 AC XY: 75459 AN XY: 610212

Gnomad4 AFR exome AF: 0.0509

Gnomad4 AMR exome AF: 0.0588

Gnomad4 ASJ exome AF: 0.0850

Gnomad4 EAS exome AF: 0.101

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.0984 AC: 14965 AN: 152154 Hom.: 895 Cov.: 32 AF XY: 0.100 AC XY: 7460 AN XY: 74384

Gnomad4 AFR AF: 0.0502

Gnomad4 AMR AF: 0.0767

Gnomad4 ASJ AF: 0.0842

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.0901

Alfa AF: 0.0777 Hom.: 145

Bravo AF: 0.0913

Asia WGS AF: 0.160 AC: 554 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.70

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: rs79948463; hg19: chr11-540604; COSMIC: COSV54243923; COSMIC: COSV54243923;