rs1913517

Positions:

• chr10-48911009-A-G
• chr10-48911009-A-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+9146A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 582,662 control chromosomes in the GnomAD database, including 74,543 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 0.54 (22581 hom., cov: 33)
  • Exomes 𝑓: 0.49 (51962 hom.)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.13

Genes affected

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]

LRRC18 (HGNC:23199): (leucine rich repeat containing 18) Predicted to be located in cytoplasm. [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 (BayesDel_noAF=-0.91).
• 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
WDFY4	NM_001394531.1	c.7586+9146A>G		intron_variant		ENST00000325239.12	NP_001381460.1
LRRC18	NM_001378102.1	c.765-751T>C		intron_variant		ENST00000374160.8	NP_001365031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDFY4	ENST00000325239.12	c.7586+9146A>G		intron_variant		5	NM_001394531.1	ENSP00000320563.5
LRRC18	ENST00000374160.8	c.765-751T>C		intron_variant		1	NM_001378102.1	ENSP00000363275.3
ENSG00000241577	ENST00000430438.1	n.173+21477T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81848 AN: 152034 Hom.: 22563 Cov.: 33

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.597

GnomAD4 exome AF: 0.491 AC: 211244 AN: 430510 Hom.: 51962 AF XY: 0.491 AC XY: 99582 AN XY: 202860

Gnomad4 AFR exome AF: 0.654

Gnomad4 AMR exome AF: 0.525

Gnomad4 ASJ exome AF: 0.627

Gnomad4 EAS exome AF: 0.760

Gnomad4 SAS exome AF: 0.622

Gnomad4 FIN exome AF: 0.556

Gnomad4 NFE exome AF: 0.480

Gnomad4 OTH exome AF: 0.546

GnomAD4 genome AF: 0.538 AC: 81907 AN: 152152 Hom.: 22581 Cov.: 33 AF XY: 0.543 AC XY: 40422 AN XY: 74380

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.593

Alfa AF: 0.499 Hom.: 45139

Bravo AF: 0.540

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.060
DANN	Benign	0.26

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: rs1913517; hg19: chr10-50119054;