10-48914136-C-T

Variant names:

• chr10-48914136-C-T
• rs7094610
• NM_001378102.1:c.20G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRRC18 NM_001378102.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• Publications: 29 publications found

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]

WDFY4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000241577 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 rank	MANE	Protein	UniProt
LRRC18	NM_001378102.1	c.20G>A	p.Gly7Asp	missense_variant	Exon 3 of 4	ENST00000374160.8	NP_001365031.1
WDFY4	NM_001394531.1	c.7586+12273C>T		intron_variant	Intron 47 of 61	ENST00000325239.12	NP_001381460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC18	ENST00000374160.8	c.20G>A	p.Gly7Asp	missense_variant	Exon 3 of 4	1	NM_001378102.1	ENSP00000363275.3
WDFY4	ENST00000325239.12	c.7586+12273C>T		intron_variant	Intron 47 of 61	5	NM_001394531.1	ENSP00000320563.5
ENSG00000241577	ENST00000430438.1	n.173+18350G>A		intron_variant	Intron 2 of 2	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
PhyloP100		0.17
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
PromoterAI		-0.051	Neutral
Varity_R		0.072
gMVP		0.45
Mutation Taster		=94/6	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: rs7094610; hg19: chr10-50122181;