chr11-62688124-G-T

Variant names:

• chr11-62688124-G-T
• rs1331814716
• NM_203422.4:c.385C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_203422.4(LRRN4CL):​c.385C>A​(p.Pro129Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. P129A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LRRN4CL NM_203422.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06666651).

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.385C>A	p.Pro129Thr	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.385C>A	p.Pro129Thr	missense	Exon 2 of 2	ENSP00000325808.4	Q8ND94
	LRRN4CL	ENST00000961805.1		c.385C>A	p.Pro129Thr	missense	Exon 2 of 2	ENSP00000631864.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460010 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726310

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111736

Other (OTH) AF: 0.00 AC: 0 AN: 60296

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.53	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.26
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.039
Sift	Benign	0.29	T
Sift4G	Benign	0.068	T
Polyphen		0.094	B
Vest4		0.13
MutPred		0.22		Loss of catalytic residue at P129 (P = 0.0525)
MVP		0.31
MPC		1.0
ClinPred		0.39	T
GERP RS		2.3
Varity_R		0.053
gMVP		0.41
Mutation Taster		=90/10	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: rs1331814716; hg19: chr11-62455596;