Genetic Variant RWDD1:c.611-16dupT (chr6-116592949-A-AT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_015952.4(RWDD1):c.611-16dupT 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 1,376,506 control chromosomes in the GnomAD database, including 1,124 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1027 hom., cov: 29)

Exomes 𝑓: 0.13 ( 97 hom. )

Consequence

RWDD1
NM_015952.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0680

Publications

2 publications found

Variant links:

Genes affected

RWDD1 (HGNC:20993): (RWD domain containing 1) Predicted to be involved in several processes, including cellular response to lipid; cytoplasmic translation; and positive regulation of androgen receptor activity. Predicted to be located in cytoplasm. Predicted to be part of polysome. [provided by Alliance of Genome Resources, Apr 2022]

RWDD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015952.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RWDD1	NM_015952.4	MANE Select	c.611-16dupT	intron	N/A	NP_057036.2
RWDD1	NM_001007464.3		c.323-16dupT	intron	N/A	NP_001007465.1
RWDD1	NM_016104.4		c.323-16dupT	intron	N/A	NP_057188.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RWDD1	ENST00000466444.7	TSL:1 MANE Select	c.611-31_611-30insT		intron	N/A	ENSP00000420357.2
	RWDD1	ENST00000487832.6	TSL:1	c.323-31_323-30insT		intron	N/A	ENSP00000428778.1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

16485

AN:

141908

Hom.:

1024

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.0244

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.0247

Gnomad SAS

AF:

0.0813

Gnomad FIN

AF:

0.0735

Gnomad MID

AF:

0.0604

Gnomad NFE

AF:

0.0966

Gnomad OTH

AF:

0.113

GnomAD2 exomes

AF:

0.140

AC:

20374

AN:

145910

AF XY:

0.134

show subpopulations

Gnomad AFR exome

AF:

0.188

Gnomad AMR exome

AF:

0.238

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.0809

Gnomad FIN exome

AF:

0.0996

Gnomad NFE exome

AF:

0.129

Gnomad OTH exome

AF:

0.127

GnomAD4 exome

AF:

0.130

AC:

160058

AN:

1234554

Hom.:

Cov.:

AF XY:

0.127

AC XY:

78284

AN XY:

617278

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.171

AC:

4757

AN:

27776

American (AMR)

AF:

0.202

AC:

7003

AN:

34752

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

2755

AN:

22266

East Asian (EAS)

AF:

0.0688

AC:

2418

AN:

35162

South Asian (SAS)

AF:

0.106

AC:

7672

AN:

72666

European-Finnish (FIN)

AF:

0.0900

AC:

3878

AN:

43080

Middle Eastern (MID)

AF:

0.0854

AC:

398

AN:

4662

European-Non Finnish (NFE)

AF:

0.132

AC:

124520

AN:

942660

Other (OTH)

AF:

0.129

AC:

6657

AN:

51530

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.352

Heterozygous variant carriers

7183

14366

21548

28731

35914

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5058

10116

15174

20232

25290

<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:

0.116

AC:

16501

AN:

141952

Hom.:

1027

Cov.:

AF XY:

0.115

AC XY:

7899

AN XY:

68802

show subpopulations

African (AFR)

AF:

0.150

AC:

5839

AN:

38812

American (AMR)

AF:

0.189

AC:

2689

AN:

14228

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

360

AN:

3340

East Asian (EAS)

AF:

0.0247

AC:

120

AN:

4852

South Asian (SAS)

AF:

0.0817

AC:

361

AN:

4418

European-Finnish (FIN)

AF:

0.0735

AC:

636

AN:

8652

Middle Eastern (MID)

AF:

0.0576

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.0966

AC:

6238

AN:

64562

Other (OTH)

AF:

0.113

AC:

221

AN:

1950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

662

1324

1985

2647

3309

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

368

552

736

920

<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:

0.0424

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.068

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over