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GeneBe

10-48914077-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001378102.1(LRRC18):c.79G>A(p.Asp27Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

LRRC18
NM_001378102.1 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.04
Variant links:
Genes affected
LRRC18 (HGNC:23199): (leucine rich repeat containing 18) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
WDFY4 (HGNC:29323): (WDFY family member 4) Predicted to be involved in autophagy. Predicted to act upstream of or within with a positive effect on CD8-positive, alpha-beta T cell activation. Predicted to act upstream of or within antigen processing and presentation and cellular response to virus. Predicted to be located in early endosome and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31879362).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LRRC18NM_001378102.1 linkuse as main transcriptc.79G>A p.Asp27Asn missense_variant 3/4 ENST00000374160.8
WDFY4NM_001394531.1 linkuse as main transcriptc.7586+12214C>T intron_variant ENST00000325239.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRRC18ENST00000374160.8 linkuse as main transcriptc.79G>A p.Asp27Asn missense_variant 3/41 NM_001378102.1 P1Q8N456-1
WDFY4ENST00000325239.12 linkuse as main transcriptc.7586+12214C>T intron_variant 5 NM_001394531.1 P1Q6ZS81-1
ENST00000430438.1 linkuse as main transcriptn.173+18409G>A intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
40
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 04, 2022The c.79G>A (p.D27N) alteration is located in exon 1 (coding exon 1) of the LRRC18 gene. This alteration results from a G to A substitution at nucleotide position 79, causing the aspartic acid (D) at amino acid position 27 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.41
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
Cadd
Uncertain
24
Dann
Uncertain
1.0
DEOGEN2
Benign
0.019
T
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.81
T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.32
T
MetaSVM
Benign
-0.67
T
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.16
Sift
Benign
0.38
T
Sift4G
Uncertain
0.0090
D
Polyphen
0.89
P
Vest4
0.29
MutPred
0.27
Gain of MoRF binding (P = 0.0658);
MVP
0.84
MPC
0.031
ClinPred
0.96
D
GERP RS
6.1
Varity_R
0.11
gMVP
0.43

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs968857991; hg19: chr10-50122122; COSMIC: COSV99628909; API