Genetic Variant WDFY4:c.7586+9146A>G (chr10-48911009-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.13

Publications

52 publications found

Variant links:

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]

WDFY4 links:

LRRC18 (HGNC:23199): (leucine rich repeat containing 18) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LRRC18 links:

ENSG00000241577 (HGNC:):

ENSG00000241577 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
WDFY4	NM_001394531.1 link	c.7586+9146A>G		intron_variant	Intron 47 of 61	ENST00000325239.12	NP_001381460.1
LRRC18	NM_001378102.1 link	c.765-751T>C		intron_variant	Intron 3 of 3	ENST00000374160.8	NP_001365031.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
WDFY4	ENST00000325239.12 link	c.7586+9146A>G	intron_variant	Intron 47 of 61	5	NM_001394531.1	ENSP00000320563.5	Q6ZS81-1
LRRC18	ENST00000374160.8 link	c.765-751T>C	intron_variant	Intron 3 of 3	1	NM_001378102.1	ENSP00000363275.3	Q8N456-1
ENSG00000241577	ENST00000430438.1 link	n.173+21477T>C	intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.538

AC:

81848

AN:

152034

Hom.:

22563

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.654

AC:

5211

AN:

7970

American (AMR)

AF:

0.525

AC:

254

AN:

484

Ashkenazi Jewish (ASJ)

AF:

0.627

AC:

1741

AN:

2778

East Asian (EAS)

AF:

0.760

AC:

1451

AN:

1908

South Asian (SAS)

AF:

0.622

AC:

5495

AN:

8828

European-Finnish (FIN)

AF:

0.556

AC:

AN:

162

Middle Eastern (MID)

AF:

0.704

AC:

603

AN:

856

European-Non Finnish (NFE)

AF:

0.480

AC:

188750

AN:

393512

Other (OTH)

AF:

0.546

AC:

7649

AN:

14012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

5273

10546

15820

21093

26366

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7670

15340

23010

30680

38350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.538

AC:

81907

AN:

152152

Hom.:

22581

Cov.:

AF XY:

0.543

AC XY:

40422

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.624

AC:

25888

AN:

41476

American (AMR)

AF:

0.505

AC:

7735

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.608

AC:

2109

AN:

3470

East Asian (EAS)

AF:

0.718

AC:

3724

AN:

5186

South Asian (SAS)

AF:

0.620

AC:

2986

AN:

4818

European-Finnish (FIN)

AF:

0.514

AC:

5437

AN:

10586

Middle Eastern (MID)

AF:

0.704

AC:

207

AN:

294

European-Non Finnish (NFE)

AF:

0.472

AC:

32112

AN:

67998

Other (OTH)

AF:

0.593

AC:

1251

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1979

3958

5937

7916

9895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

714

1428

2142

2856

3570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.496

Hom.:

90097

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

(source)

DANN

Benign

0.26

PhyloP100

-3.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over