11-62687823-C-G

Variant names:

• chr11-62687823-C-G
• rs1377674796
• NM_203422.4:c.686G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203422.4(LRRN4CL):​c.686G>C​(p.Arg229Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000161 in 1,245,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R229Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: LRRN4CL NM_203422.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.771
• Publications: 0 publications found

Genes affected

LRRN4CL (HGNC:33724): (LRRN4 C-terminal like) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24976775).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203422.4. 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
	LRRN4CL	NM_203422.4	MANE Select	c.686G>C	p.Arg229Pro	missense	Exon 2 of 2	NP_981967.1	Q8ND94

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRN4CL	ENST00000317449.5	TSL:1 MANE Select	c.686G>C	p.Arg229Pro	missense	Exon 2 of 2	ENSP00000325808.4	Q8ND94
	LRRN4CL	ENST00000961805.1		c.686G>C	p.Arg229Pro	missense	Exon 2 of 2	ENSP00000631864.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000161 AC: 2 AN: 1245364 Hom.: 0 Cov.: 31 AF XY: 0.00000331 AC XY: 2 AN XY: 604292

African (AFR) AF: 0.00 AC: 0 AN: 23858

American (AMR) AF: 0.00 AC: 0 AN: 12834

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17392

East Asian (EAS) AF: 0.0000335 AC: 1 AN: 29884

South Asian (SAS) AF: 0.00 AC: 0 AN: 56660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30782

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3698

European-Non Finnish (NFE) AF: 9.81e-7 AC: 1 AN: 1018858

Other (OTH) AF: 0.00 AC: 0 AN: 51398

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Benign	0.061
Eigen_PC	Benign	-0.024
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.77
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.13
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.060	T
Polyphen		1.0	D
Vest4		0.30
MutPred		0.47		Loss of MoRF binding (P = 2e-04)
MVP		0.39
MPC		0.44
ClinPred		0.90	D
GERP RS		3.5
Varity_R		0.18
gMVP		0.41
Mutation Taster		=86/14	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

Other links and lift over

dbSNP: rs1377674796; hg19: chr11-62455295;