Genetic Variant NM_016084.5:c.*621C>G (chr17-17494504-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_016084.5(RASD1):c.*621C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 151,206 control chromosomes in the GnomAD database, including 35,894 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 ( 35773 hom., cov: 28)

Exomes 𝑓: 0.73 ( 121 hom. )

Consequence

RASD1
NM_016084.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.380

Publications

10 publications found

Variant links:

Genes affected

RASD1 (HGNC:15828): (ras related dexamethasone induced 1) This gene encodes a member of the Ras superfamily of small GTPases and is induced by dexamethasone. The encoded protein is an activator of G-protein signaling and acts as a direct nucleotide exchange factor for Gi-Go proteins. This protein interacts with the neuronal nitric oxide adaptor protein CAPON, and a nuclear adaptor protein FE65, which interacts with the Alzheimer's disease amyloid precursor protein. This gene may play a role in dexamethasone-induced alterations in cell morphology, growth and cell-extracellular matrix interactions. Epigenetic inactivation of this gene is closely correlated with resistance to dexamethasone in multiple myeloma cells. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2011]

RASD1 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 (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASD1	NM_016084.5 link	c.*621C>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000225688.4	NP_057168.1	Q9Y272-1
RASD1	NM_001199989.2 link	c.*1024C>G		3_prime_UTR_variant	Exon 2 of 2		NP_001186918.1	Q9Y272-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASD1	ENST00000225688.4 link	c.*621C>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_016084.5	ENSP00000225688.3		Q9Y272-1
RASD1	ENST00000579152.1 link	c.*1024C>G		downstream_gene_variant		2		ENSP00000463388.1		Q9Y272-2

Frequencies

GnomAD3 genomes

AF:

0.683

AC:

102925

AN:

150650

Hom.:

35755

Cov.:

show subpopulations

Gnomad AFR

AF:

0.644

Gnomad AMI

AF:

0.660

Gnomad AMR

AF:

0.623

Gnomad ASJ

AF:

0.692

Gnomad EAS

AF:

0.259

Gnomad SAS

AF:

0.558

Gnomad FIN

AF:

0.704

Gnomad MID

AF:

0.706

Gnomad NFE

AF:

0.758

Gnomad OTH

AF:

0.681

GnomAD4 exome

AF:

0.725

AC:

322

AN:

444

Hom.:

121

Cov.:

AF XY:

0.743

AC XY:

199

AN XY:

268

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.333

AC:

AN:

European-Finnish (FIN)

AF:

0.721

AC:

274

AN:

380

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.813

AC:

AN:

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.683

AC:

102999

AN:

150762

Hom.:

35773

Cov.:

AF XY:

0.677

AC XY:

49768

AN XY:

73566

show subpopulations

African (AFR)

AF:

0.643

AC:

26253

AN:

40798

American (AMR)

AF:

0.624

AC:

9449

AN:

15146

Ashkenazi Jewish (ASJ)

AF:

0.692

AC:

2395

AN:

3460

East Asian (EAS)

AF:

0.260

AC:

1323

AN:

5096

South Asian (SAS)

AF:

0.558

AC:

2671

AN:

4784

European-Finnish (FIN)

AF:

0.704

AC:

7261

AN:

10312

Middle Eastern (MID)

AF:

0.713

AC:

204

AN:

286

European-Non Finnish (NFE)

AF:

0.758

AC:

51420

AN:

67872

Other (OTH)

AF:

0.678

AC:

1422

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1536

3072

4607

6143

7679

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<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:

0.655

Hom.:

1997

Bravo

AF:

0.673

Asia WGS

AF:

0.448

AC:

1559

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.6

(source)

DANN

Benign

0.71

PhyloP100

-0.38

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