10-48914136-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001378102.1(LRRC18):c.20G>A(p.Gly7Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. G7V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRRC18 NM_001378102.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169

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]

(HGNC:):

ACMG classification

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=0.3201459).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC18	NM_001378102.1	c.20G>A	p.Gly7Asp	missense_variant	3/4	ENST00000374160.8
WDFY4	NM_001394531.1	c.7586+12273C>T		intron_variant		ENST00000325239.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC18	ENST00000374160.8	c.20G>A	p.Gly7Asp	missense_variant	3/4	1	NM_001378102.1	P1
WDFY4	ENST00000325239.12	c.7586+12273C>T		intron_variant		5	NM_001394531.1	P1
	ENST00000430438.1	n.173+18350G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	6.7
Dann	Benign	0.53
DEOGEN2	Benign	0.085	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	0.22	P;P;P;P
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.10
Sift	Benign	0.60	T
Sift4G	Benign	0.25	T
Polyphen		0.88	P
Vest4		0.34
MutPred		0.37		Loss of MoRF binding (P = 0.0237);
MVP		0.54
MPC		0.017
ClinPred		0.18	T
GERP RS		0.75
Varity_R		0.072
gMVP		0.45

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: rs7094610; hg19: chr10-50122181;