Genetic Variant GRWD1:p.Arg8Arg (chr19-48446029-G-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_031485.4(GRWD1):c.24G>T(p.Arg8Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 1,591,636 control chromosomes in the GnomAD database, including 611,520 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 0.80 ( 50241 hom., cov: 31)

Exomes 𝑓: 0.88 ( 561279 hom. )

Consequence

GRWD1
NM_031485.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.294

Publications

24 publications found

Variant links:

Genes affected

GRWD1 (HGNC:21270): (glutamate rich WD repeat containing 1) This gene encodes a glutamate-rich protein that contains five WD-repeat motifs. The encoded protein may play a critical role in ribosome biogenesis and may also play a role in histone methylation through interactions with CUL4-DDB1 ubiquitin E3 ligase. [provided by RefSeq, Feb 2012]

GRWD1 Gene-Disease associations (from GenCC):

congenital diarrhea
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

GRWD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP7

Synonymous conserved (PhyloP=0.294 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRWD1	NM_031485.4 link	c.24G>T	p.Arg8Arg	synonymous_variant	Exon 1 of 7	ENST00000253237.10	NP_113673.3	Q9BQ67

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GRWD1	ENST00000253237.10 link	c.24G>T	p.Arg8Arg	synonymous_variant	Exon 1 of 7	1	NM_031485.4	ENSP00000253237.4	Q9BQ67
GRWD1	ENST00000599949.1 link	n.38G>T		non_coding_transcript_exon_variant	Exon 1 of 2	4
GRWD1	ENST00000598711.1 link	c.-123+115G>T		intron_variant	Intron 1 of 5	3		ENSP00000468943.1	M0QX71

Frequencies

GnomAD3 genomes

AF:

0.801

AC:

121654

AN:

151828

Hom.:

50220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.604

Gnomad AMI

AF:

0.948

Gnomad AMR

AF:

0.835

Gnomad ASJ

AF:

0.939

Gnomad EAS

AF:

0.595

Gnomad SAS

AF:

0.787

Gnomad FIN

AF:

0.881

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.908

Gnomad OTH

AF:

0.817

GnomAD2 exomes

AF:

0.835

AC:

177101

AN:

212062

AF XY:

0.839

show subpopulations

Gnomad AFR exome

AF:

0.598

Gnomad AMR exome

AF:

0.821

Gnomad ASJ exome

AF:

0.938

Gnomad EAS exome

AF:

0.597

Gnomad FIN exome

AF:

0.878

Gnomad NFE exome

AF:

0.907

Gnomad OTH exome

AF:

0.870

GnomAD4 exome

AF:

0.879

AC:

1265987

AN:

1439690

Hom.:

561279

Cov.:

AF XY:

0.878

AC XY:

626887

AN XY:

714212

show subpopulations

African (AFR)

AF:

0.592

AC:

19603

AN:

33098

American (AMR)

AF:

0.826

AC:

33834

AN:

40970

Ashkenazi Jewish (ASJ)

AF:

0.935

AC:

23955

AN:

25624

East Asian (EAS)

AF:

0.559

AC:

21714

AN:

38816

South Asian (SAS)

AF:

0.788

AC:

65420

AN:

82998

European-Finnish (FIN)

AF:

0.877

AC:

45129

AN:

51460

Middle Eastern (MID)

AF:

0.866

AC:

3879

AN:

4480

European-Non Finnish (NFE)

AF:

0.908

AC:

1001573

AN:

1102774

Other (OTH)

AF:

0.856

AC:

50880

AN:

59470

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

8232

16464

24696

32928

41160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.801

AC:

121722

AN:

151946

Hom.:

50241

Cov.:

AF XY:

0.798

AC XY:

59292

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.604

AC:

25036

AN:

41432

American (AMR)

AF:

0.835

AC:

12746

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.939

AC:

3259

AN:

3472

East Asian (EAS)

AF:

0.594

AC:

3057

AN:

5150

South Asian (SAS)

AF:

0.788

AC:

3789

AN:

4806

European-Finnish (FIN)

AF:

0.881

AC:

9307

AN:

10560

Middle Eastern (MID)

AF:

0.888

AC:

261

AN:

294

European-Non Finnish (NFE)

AF:

0.908

AC:

61675

AN:

67938

Other (OTH)

AF:

0.818

AC:

1729

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1080

2159

3239

4318

5398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.881

Hom.:

55146

Bravo

AF:

0.790

Asia WGS

AF:

0.685

AC:

2384

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

8.6

(source)

DANN

Benign

0.93

PhyloP100

0.29

PromoterAI

0.028

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

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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19-48446029-G-T

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