rs79948463

Variant names:

• chr11-540604-A-C
• rs79948463
• NM_198075.4:c.-11-70A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-540604-A-C
• chr11-540604-A-G
• chr11-540604-A-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.-11-70A>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
• Publications: 3 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: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• 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=-0.86).
• BP6: Variant 11-540604-A-C is Benign according to our data. Variant chr11-540604-A-C is described in ClinVar as Benign. ClinVar VariationId 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.

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.-11-70A>C		intron	N/A	NP_932341.1	Q8IYG6
	LRRC56	NM_001441283.1		c.-14-67A>C		intron	N/A	NP_001428212.1
	LRRC56	NM_001441284.1		c.-14-67A>C		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.-11-70A>C		intron	N/A	ENSP00000270115.7	Q8IYG6
	LRRC56	ENST00000886180.1		c.-14-67A>C		intron	N/A	ENSP00000556239.1
	LRRC56	ENST00000886182.1		c.-11-70A>C		intron	N/A	ENSP00000556241.1

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

African (AFR) AF: 0.0509 AC: 1427 AN: 28052

American (AMR) AF: 0.0588 AC: 1946 AN: 33108

Ashkenazi Jewish (ASJ) AF: 0.0850 AC: 1961 AN: 23072

East Asian (EAS) AF: 0.101 AC: 3630 AN: 35860

South Asian (SAS) AF: 0.178 AC: 13385 AN: 74996

European-Finnish (FIN) AF: 0.132 AC: 5834 AN: 44276

Middle Eastern (MID) AF: 0.110 AC: 477 AN: 4346

European-Non Finnish (NFE) AF: 0.124 AC: 114599 AN: 927310

Other (OTH) AF: 0.110 AC: 5695 AN: 51982

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

African (AFR) AF: 0.0502 AC: 2084 AN: 41546

American (AMR) AF: 0.0767 AC: 1172 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0842 AC: 292 AN: 3468

East Asian (EAS) AF: 0.126 AC: 650 AN: 5172

South Asian (SAS) AF: 0.185 AC: 890 AN: 4816

European-Finnish (FIN) AF: 0.117 AC: 1241 AN: 10590

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

European-Non Finnish (NFE) AF: 0.121 AC: 8216 AN: 67968

Other (OTH) AF: 0.0901 AC: 190 AN: 2108

Alfa AF: 0.0763 Hom.: 280

Bravo AF: 0.0913

Asia WGS AF: 0.160 AC: 554 AN: 3478

ClinVar

ClinVar submissions

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	-0.86
CADD	Benign	2.2
DANN	Benign	0.70
PhyloP100		-1.3
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: rs79948463; hg19: chr11-540604; COSMIC: COSV54243923; COSMIC: COSV54243923;