dbSNP rs292592: WDR91:p.Pro257Leu (chr7-135204389-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_014149.4(WDR91):c.770C>T(p.Pro257Leu) variant causes a missense change. The variant allele was found at a frequency of 0.721 in 1,613,788 control chromosomes in the GnomAD database, including 422,427 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 0.68 ( 35855 hom., cov: 32)

Exomes 𝑓: 0.73 ( 386572 hom. )

Consequence

WDR91
NM_014149.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.50

Publications

46 publications found

Variant links:

Genes affected

WDR91 (HGNC:24997): (WD repeat domain 91) Enables phosphatidylinositol 3-kinase regulator activity. Involved in early endosome to late endosome transport; regulation of cellular protein catabolic process; and regulation of phosphatidylinositol 3-kinase activity. Located in cytosol; early endosome membrane; and late endosome membrane. Is extrinsic component of endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

WDR91 links:

ENSG00000231794 (HGNC:):

ENSG00000231794 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=1.1990732E-6).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR91	NM_014149.4 link	c.770C>T	p.Pro257Leu	missense_variant	Exon 6 of 15	ENST00000354475.5	NP_054868.3	A4D1P6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR91	ENST00000354475.5 link	c.770C>T	p.Pro257Leu	missense_variant	Exon 6 of 15	1	NM_014149.4	ENSP00000346466.4		A4D1P6-1
WDR91	ENST00000423565.5 link	c.665C>T	p.Pro222Leu	missense_variant	Exon 6 of 15	5		ENSP00000392555.1		C9J1X0

Frequencies

GnomAD3 genomes

AF:

0.680

AC:

103323

AN:

151950

Hom.:

35836

Cov.:

show subpopulations

Gnomad AFR

AF:

0.534

Gnomad AMI

AF:

0.845

Gnomad AMR

AF:

0.792

Gnomad ASJ

AF:

0.727

Gnomad EAS

AF:

0.593

Gnomad SAS

AF:

0.738

Gnomad FIN

AF:

0.734

Gnomad MID

AF:

0.761

Gnomad NFE

AF:

0.731

Gnomad OTH

AF:

0.728

GnomAD2 exomes

AF:

0.720

AC:

180594

AN:

250966

AF XY:

0.722

show subpopulations

Gnomad AFR exome

AF:

0.527

Gnomad AMR exome

AF:

0.821

Gnomad ASJ exome

AF:

0.734

Gnomad EAS exome

AF:

0.582

Gnomad FIN exome

AF:

0.724

Gnomad NFE exome

AF:

0.730

Gnomad OTH exome

AF:

0.729

GnomAD4 exome

AF:

0.726

AC:

1060762

AN:

1461720

Hom.:

386572

Cov.:

AF XY:

0.727

AC XY:

528299

AN XY:

727164

show subpopulations

African (AFR)

AF:

0.523

AC:

17495

AN:

33478

American (AMR)

AF:

0.820

AC:

36679

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.731

AC:

19116

AN:

26134

East Asian (EAS)

AF:

0.598

AC:

23735

AN:

39692

South Asian (SAS)

AF:

0.738

AC:

63651

AN:

86238

European-Finnish (FIN)

AF:

0.728

AC:

38873

AN:

53392

Middle Eastern (MID)

AF:

0.713

AC:

4113

AN:

5768

European-Non Finnish (NFE)

AF:

0.732

AC:

813813

AN:

1111920

Other (OTH)

AF:

0.717

AC:

43287

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

15971

31942

47913

63884

79855

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20052

40104

60156

80208

100260

<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:

0.680

AC:

103389

AN:

152068

Hom.:

35855

Cov.:

AF XY:

0.681

AC XY:

50589

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.534

AC:

22155

AN:

41464

American (AMR)

AF:

0.793

AC:

12118

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.727

AC:

2524

AN:

3472

East Asian (EAS)

AF:

0.592

AC:

3049

AN:

5152

South Asian (SAS)

AF:

0.737

AC:

3556

AN:

4824

European-Finnish (FIN)

AF:

0.734

AC:

7765

AN:

10580

Middle Eastern (MID)

AF:

0.753

AC:

220

AN:

292

European-Non Finnish (NFE)

AF:

0.731

AC:

49696

AN:

67986

Other (OTH)

AF:

0.730

AC:

1535

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1660

3321

4981

6642

8302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

814

1628

2442

3256

4070

<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:

0.714

Hom.:

131122

Bravo

AF:

0.678

TwinsUK

AF:

0.744

AC:

2760

ALSPAC

AF:

0.727

AC:

2803

ESP6500AA

AF:

0.550

AC:

2423

ESP6500EA

AF:

0.724

AC:

6223

ExAC

AF:

0.713

AC:

86547

Asia WGS

AF:

0.690

AC:

2397

AN:

3478

EpiCase

AF:

0.729

EpiControl

AF:

0.732

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

T;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.70

T;T

MetaRNN

Benign

0.0000012

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

.;L

PhyloP100

6.5

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.5

N;D

REVEL

Benign

0.15

Sift

Benign

0.23

T;T

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.90

.;P

Vest4

0.12

MPC

0.57

ClinPred

0.014

GERP RS

5.4

Varity_R

0.14

gMVP

0.17

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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