10-48923352-G-C

Variant names:

• chr10-48923352-G-C
• rs10745288
• NM_001394531.1:c.7587-18454G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394531.1(WDFY4):​c.7587-18454G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 151,056 control chromosomes in the GnomAD database, including 23,540 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 0.52 (23540 hom., cov: 29)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394531.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	NM_001394531.1	MANE Select	c.7587-18454G>C		intron	N/A	NP_001381460.1	Q6ZS81-1
	LRRC18	NM_001378102.1	MANE Select	c.-77-9120C>G		intron	N/A	NP_001365031.1	Q8N456-1
	WDFY4	NM_020945.2		c.7587-18454G>C		intron	N/A	NP_065996.1	Q6ZS81-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	ENST00000325239.12	TSL:5 MANE Select	c.7587-18454G>C		intron	N/A	ENSP00000320563.5	Q6ZS81-1
	LRRC18	ENST00000374160.8	TSL:1 MANE Select	c.-77-9120C>G		intron	N/A	ENSP00000363275.3	Q8N456-1
	WDFY4	ENST00000858472.1		c.7587-18454G>C		intron	N/A	ENSP00000528531.1

Frequencies

GnomAD3 genomes AF: 0.516 AC: 77882 AN: 150938 Hom.: 23533 Cov.: 29

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.516 AC: 77899 AN: 151056 Hom.: 23540 Cov.: 29 AF XY: 0.530 AC XY: 39058 AN XY: 73722

African (AFR) AF: 0.197 AC: 8144 AN: 41310

American (AMR) AF: 0.669 AC: 10097 AN: 15102

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2117 AN: 3448

East Asian (EAS) AF: 0.996 AC: 5094 AN: 5116

South Asian (SAS) AF: 0.736 AC: 3509 AN: 4768

European-Finnish (FIN) AF: 0.680 AC: 7057 AN: 10376

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.591 AC: 39969 AN: 67638

Other (OTH) AF: 0.582 AC: 1217 AN: 2092

Alfa AF: 0.530 Hom.: 2584

Bravo AF: 0.501

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.3
DANN	Benign	0.77
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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: rs10745288; hg19: chr10-50131397;