chr10-48913380-G-C

Variant names:

• chr10-48913380-G-C
• rs12774010
• NM_001394531.1:c.7586+11517G>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.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
• Publications: 3 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=-0.48).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	NM_001394531.1	MANE Select	c.7586+11517G>C		intron	N/A	NP_001381460.1
	LRRC18	NM_001378102.1	MANE Select	c.764+12C>G		intron	N/A	NP_001365031.1
	WDFY4	NM_020945.2		c.7586+11517G>C		intron	N/A	NP_065996.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	ENST00000325239.12	TSL:5 MANE Select	c.7586+11517G>C		intron	N/A	ENSP00000320563.5
	LRRC18	ENST00000374160.8	TSL:1 MANE Select	c.764+12C>G		intron	N/A	ENSP00000363275.3
	ENSG00000241577	ENST00000430438.1	TSL:5	n.173+19106C>G		intron	N/A

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

GnomAD2 exomes AF: 0.121 AC: 29514 AN: 244604 AF XY: 0.126

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 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

African (AFR) AF: 0.180 AC: 6014 AN: 33324

American (AMR) AF: 0.0751 AC: 3343 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 4848 AN: 25986

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39654

South Asian (SAS) AF: 0.171 AC: 14717 AN: 86158

European-Finnish (FIN) AF: 0.133 AC: 6530 AN: 49010

Middle Eastern (MID) AF: 0.207 AC: 1187 AN: 5746

European-Non Finnish (NFE) AF: 0.126 AC: 139835 AN: 1109204

Other (OTH) AF: 0.131 AC: 7877 AN: 60182

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

African (AFR) AF: 0.174 AC: 7205 AN: 41332

American (AMR) AF: 0.102 AC: 1557 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 637 AN: 3470

East Asian (EAS) AF: 0.00194 AC: 10 AN: 5150

South Asian (SAS) AF: 0.163 AC: 779 AN: 4780

European-Finnish (FIN) AF: 0.140 AC: 1474 AN: 10532

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.126 AC: 8587 AN: 67944

Other (OTH) AF: 0.133 AC: 280 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.67
PhyloP100		1.9
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12774010; hg19: chr10-50121425;