10-48911009-A-T

Variant names:

• chr10-48911009-A-T
• rs1913517
• NM_001394531.1:c.7586+9146A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001394531.1(WDFY4):​c.7586+9146A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000231 in 432,136 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.13
• Publications: 52 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDFY4	NM_001394531.1	c.7586+9146A>T		intron_variant	Intron 47 of 61	ENST00000325239.12	NP_001381460.1
LRRC18	NM_001378102.1	c.765-751T>A		intron_variant	Intron 3 of 3	ENST00000374160.8	NP_001365031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDFY4	ENST00000325239.12	c.7586+9146A>T		intron_variant	Intron 47 of 61	5	NM_001394531.1	ENSP00000320563.5
LRRC18	ENST00000374160.8	c.765-751T>A		intron_variant	Intron 3 of 3	1	NM_001378102.1	ENSP00000363275.3
ENSG00000241577	ENST00000430438.1	n.173+21477T>A		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000231 AC: 1 AN: 432136 Hom.: 0 AF XY: 0.00000491 AC XY: 1 AN XY: 203622

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 7996

American (AMR) AF: 0.00 AC: 0 AN: 486

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2780

East Asian (EAS) AF: 0.00 AC: 0 AN: 1914

South Asian (SAS) AF: 0.00 AC: 0 AN: 8854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 858

European-Non Finnish (NFE) AF: 0.00000253 AC: 1 AN: 395004

Other (OTH) AF: 0.00 AC: 0 AN: 14082

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.051
DANN	Benign	0.49
PhyloP100		-3.1

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: rs1913517; hg19: chr10-50119054;