rs12774010

Positions:

• chr10-48913380-G-C
• chr10-48913380-G-T

Variant summary

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

The NM_001394531.1(WDFY4):​c.7586+11517G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,605,578 control chromosomes in the GnomAD database, including 14,229 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1575 hom., cov: 30)
  • Exomes 𝑓: 0.13 (12654 hom.)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC18	NM_001378102.1	c.764+12C>G		intron_variant		ENST00000374160.8
WDFY4	NM_001394531.1	c.7586+11517G>C		intron_variant		ENST00000325239.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDFY4	ENST00000325239.12	c.7586+11517G>C		intron_variant		5	NM_001394531.1	P1
LRRC18	ENST00000374160.8	c.764+12C>G		intron_variant		1	NM_001378102.1	P1
	ENST00000430438.1	n.173+19106C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20676 AN: 151658 Hom.: 1571 Cov.: 30

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.00194

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.134

GnomAD3 exomes AF: 0.121 AC: 29514 AN: 244604 Hom.: 2167 AF XY: 0.126 AC XY: 16672 AN XY: 132580

Gnomad AFR exome AF: 0.178

Gnomad AMR exome AF: 0.0718

Gnomad ASJ exome AF: 0.185

Gnomad EAS exome AF: 0.000327

Gnomad SAS exome AF: 0.173

Gnomad FIN exome AF: 0.135

Gnomad NFE exome AF: 0.124

Gnomad OTH exome AF: 0.140

GnomAD4 exome AF: 0.127 AC: 184362 AN: 1453802 Hom.: 12654 Cov.: 32 AF XY: 0.129 AC XY: 93219 AN XY: 723018

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.0751

Gnomad4 ASJ exome AF: 0.187

Gnomad4 EAS exome AF: 0.000277

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.136 AC: 20689 AN: 151776 Hom.: 1575 Cov.: 30 AF XY: 0.136 AC XY: 10062 AN XY: 74162

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.00194

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.133

Alfa AF: 0.141 Hom.: 291

Bravo AF: 0.135

Asia WGS AF: 0.0770 AC: 270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs12774010; hg19: chr10-50121425;