rs202242349

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_015275.3(WASHC4):c.2700A>C(p.Gly900Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,607,930 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0026 ( 8 hom. )

Consequence

WASHC4
NM_015275.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.35

Publications

2 publications found

Variant links:

Genes affected

WASHC4 (HGNC:29174): (WASH complex subunit 4) This gene encodes a component of the WASH complex, which functions in the intracellular transport of endosomes. Mutations in this gene have been detected in individuals with autosomal recessive cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

WASHC4 Gene-Disease associations (from GenCC):

autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
intellectual disability, autosomal recessive 43
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

WASHC4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 12-105152393-A-C is Benign according to our data. Variant chr12-105152393-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 435582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.35 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00146 (223/152288) while in subpopulation NFE AF = 0.00243 (165/68010). AF 95% confidence interval is 0.00212. There are 0 homozygotes in GnomAd4. There are 110 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 8 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WASHC4	NM_015275.3 link	c.2700A>C	p.Gly900Gly	synonymous_variant	Exon 26 of 33	ENST00000332180.10	NP_056090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WASHC4	ENST00000332180.10 link	c.2700A>C	p.Gly900Gly	synonymous_variant	Exon 26 of 33	1	NM_015275.3	ENSP00000328062.6

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

223

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00243

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00144

AC:

359

AN:

249268

AF XY:

0.00148

show subpopulations

Gnomad AFR exome

AF:

0.000904

Gnomad AMR exome

AF:

0.000551

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00204

Gnomad NFE exome

AF:

0.00239

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.00260

AC:

3788

AN:

1455642

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

1785

AN XY:

724684

show subpopulations

African (AFR)

AF:

0.000780

AC:

AN:

33320

American (AMR)

AF:

0.000559

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26078

East Asian (EAS)

AF:

0.00

AC:

AN:

39622

South Asian (SAS)

AF:

0.0000581

AC:

AN:

86126

European-Finnish (FIN)

AF:

0.00169

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00122

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00315

AC:

3489

AN:

1106436

Other (OTH)

AF:

0.00243

AC:

146

AN:

60178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

162

324

487

649

811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

288

432

576

720

<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:

0.00146

AC:

223

AN:

152288

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

110

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.000674

AC:

AN:

41562

American (AMR)

AF:

0.000980

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00243

AC:

165

AN:

68010

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00213

Hom.:

Bravo

AF:

0.00155

EpiCase

AF:

0.00376

EpiControl

AF:

0.00261

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

WASHC4: BP4 -

Jul 06, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Dec 02, 2016

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

8.7

(source)

DANN

Benign

0.74

PhyloP100

3.3

PromoterAI

0.036

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over