rs7094610

Positions:

• chr10-48914136-C-A
• chr10-48914136-C-G
• chr10-48914136-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378102.1(LRRC18):​c.20G>T​(p.Gly7Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,613,084 control chromosomes in the GnomAD database, including 99,512 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.29 (7864 hom., cov: 33)
  • Exomes 𝑓: 0.34 (91648 hom.)
• 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]

ENSG00000241577 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.3019155E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC18	NM_001378102.1	c.20G>T	p.Gly7Val	missense_variant	3/4	ENST00000374160.8	NP_001365031.1
WDFY4	NM_001394531.1	c.7586+12273C>A		intron_variant		ENST00000325239.12	NP_001381460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC18	ENST00000374160.8	c.20G>T	p.Gly7Val	missense_variant	3/4	1	NM_001378102.1	ENSP00000363275.3
WDFY4	ENST00000325239.12	c.7586+12273C>A		intron_variant		5	NM_001394531.1	ENSP00000320563.5
ENSG00000241577	ENST00000430438.1	n.173+18350G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44609 AN: 151928 Hom.: 7866 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.347

GnomAD3 exomes AF: 0.358 AC: 89678 AN: 250498 Hom.: 18050 AF XY: 0.366 AC XY: 49528 AN XY: 135398

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.300

Gnomad ASJ exome AF: 0.377

Gnomad EAS exome AF: 0.719

Gnomad SAS exome AF: 0.421

Gnomad FIN exome AF: 0.340

Gnomad NFE exome AF: 0.339

Gnomad OTH exome AF: 0.353

GnomAD4 exome AF: 0.344 AC: 502909 AN: 1461038 Hom.: 91648 Cov.: 40 AF XY: 0.347 AC XY: 252445 AN XY: 726798

Gnomad4 AFR exome AF: 0.0978

Gnomad4 AMR exome AF: 0.302

Gnomad4 ASJ exome AF: 0.375

Gnomad4 EAS exome AF: 0.740

Gnomad4 SAS exome AF: 0.416

Gnomad4 FIN exome AF: 0.337

Gnomad4 NFE exome AF: 0.332

Gnomad4 OTH exome AF: 0.363

GnomAD4 genome AF: 0.293 AC: 44595 AN: 152046 Hom.: 7864 Cov.: 33 AF XY: 0.301 AC XY: 22335 AN XY: 74304

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.346

Alfa AF: 0.345 Hom.: 21816

Bravo AF: 0.282

TwinsUK AF: 0.334 AC: 1237

ALSPAC AF: 0.331 AC: 1276

ESP6500AA AF: 0.113 AC: 499

ESP6500EA AF: 0.346 AC: 2973

ExAC AF: 0.354 AC: 42940

Asia WGS AF: 0.521 AC: 1815 AN: 3478

EpiCase AF: 0.351

EpiControl AF: 0.348

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.69
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0000013	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.055
Sift	Benign	0.28	T
Sift4G	Benign	0.23	T
Polyphen		0.034	B
Vest4		0.075
MPC		0.017
ClinPred		0.0041	T
GERP RS		0.75
Varity_R		0.084
gMVP		0.47

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; COSMIC: COSV53282836;