rs2663056

chr10-48917927-C-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+16064C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,124 control chromosomes in the GnomAD database, including 3,506 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 0.20 (3506 hom., cov: 33)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC18	NM_001378102.1	c.-77-3695G>A		intron_variant		ENST00000374160.8
WDFY4	NM_001394531.1	c.7586+16064C>T		intron_variant		ENST00000325239.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDFY4	ENST00000325239.12	c.7586+16064C>T		intron_variant		5	NM_001394531.1	P1
LRRC18	ENST00000374160.8	c.-77-3695G>A		intron_variant		1	NM_001378102.1	P1
	ENST00000430438.1	n.173+14559G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30933 AN: 152006 Hom.: 3506 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.0810

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.176

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.203 AC: 30934 AN: 152124 Hom.: 3506 Cov.: 33 AF XY: 0.197 AC XY: 14657 AN XY: 74354

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0813

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.174

Alfa AF: 0.242 Hom.: 9311

Bravo AF: 0.197

Asia WGS AF: 0.0590 AC: 206 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	6.2
Dann	Benign	0.76

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: rs2663056; hg19: chr10-50125972;