Genetic Variant RHOD:p.Asp88Asp (chr11-67066781-C-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_014578.4(RHOD):c.264C>T(p.Asp88Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,611,384 control chromosomes in the GnomAD database, including 114,190 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 0.33 ( 9132 hom., cov: 33)

Exomes 𝑓: 0.37 ( 105058 hom. )

Consequence

RHOD
NM_014578.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.57

Publications

25 publications found

Variant links:

Genes affected

RHOD (HGNC:670): (ras homolog family member D) Ras homolog, or Rho, proteins interact with protein kinases and may serve as targets for activated GTPase. They play a critical role in muscle differentiation. The protein encoded by this gene binds GTP and is a member of the small GTPase superfamily. It is involved in endosome dynamics and reorganization of the actin cytoskeleton, and it may coordinate membrane transport with the function of the cytoskeleton. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

RHOD links:

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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=-0.84).

BP7

Synonymous conserved (PhyloP=-4.57 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOD	NM_014578.4 link	c.264C>T	p.Asp88Asp	synonymous_variant	Exon 3 of 5	ENST00000308831.7	NP_055393.1
RHOD	NM_001300886.2 link	c.133-3644C>T		intron_variant	Intron 1 of 2		NP_001287815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
RHOD	ENST00000308831.7 link	c.264C>T	p.Asp88Asp	synonymous_variant	Exon 3 of 5	1	NM_014578.4	ENSP00000308576.2
RHOD	ENST00000533360.2 link	n.307C>T		non_coding_transcript_exon_variant	Exon 3 of 4	2
RHOD	ENST00000532559.1 link	c.133-3644C>T		intron_variant	Intron 1 of 2	3		ENSP00000432003.1

Frequencies

GnomAD3 genomes

AF:

0.329

AC:

50052

AN:

152074

Hom.:

9135

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.405

Gnomad AMR

AF:

0.481

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.463

Gnomad SAS

AF:

0.515

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.356

GnomAD2 exomes

AF:

0.400

AC:

100562

AN:

251390

AF XY:

0.398

show subpopulations

Gnomad AFR exome

AF:

0.183

Gnomad AMR exome

AF:

0.597

Gnomad ASJ exome

AF:

0.405

Gnomad EAS exome

AF:

0.457

Gnomad FIN exome

AF:

0.277

Gnomad NFE exome

AF:

0.359

Gnomad OTH exome

AF:

0.390

GnomAD4 exome

AF:

0.372

AC:

543073

AN:

1459192

Hom.:

105058

Cov.:

AF XY:

0.375

AC XY:

271909

AN XY:

725998

show subpopulations

African (AFR)

AF:

0.179

AC:

5976

AN:

33448

American (AMR)

AF:

0.587

AC:

26232

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.411

AC:

10735

AN:

26128

East Asian (EAS)

AF:

0.466

AC:

18486

AN:

39674

South Asian (SAS)

AF:

0.494

AC:

42581

AN:

86196

European-Finnish (FIN)

AF:

0.282

AC:

15058

AN:

53356

Middle Eastern (MID)

AF:

0.401

AC:

2314

AN:

5768

European-Non Finnish (NFE)

AF:

0.359

AC:

398900

AN:

1109596

Other (OTH)

AF:

0.378

AC:

22791

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

18090

36179

54269

72358

90448

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12814

25628

38442

51256

64070

<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:

0.329

AC:

50060

AN:

152192

Hom.:

9132

Cov.:

AF XY:

0.332

AC XY:

24727

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.188

AC:

7797

AN:

41552

American (AMR)

AF:

0.481

AC:

7353

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.419

AC:

1453

AN:

3466

East Asian (EAS)

AF:

0.464

AC:

2390

AN:

5156

South Asian (SAS)

AF:

0.515

AC:

2486

AN:

4828

European-Finnish (FIN)

AF:

0.276

AC:

2927

AN:

10608

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.359

AC:

24418

AN:

67976

Other (OTH)

AF:

0.360

AC:

760

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

1614

3228

4843

6457

8071

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

500

1000

1500

2000

2500

<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:

0.344

Hom.:

4817

Bravo

AF:

0.340

Asia WGS

AF:

0.441

AC:

1536

AN:

3478

EpiCase

AF:

0.365

EpiControl

AF:

0.368

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.48

(source)

DANN

Benign

0.35

PhyloP100

-4.6

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