Genetic Variant RSU1:c.599-4_599-3dupCC (chr10-16695157-T-TGG) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_012425.4(RSU1):c.599-4_599-3dupCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,201,784 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 17)

Exomes 𝑓: 0.00089 ( 4 hom. )

Consequence

RSU1
NM_012425.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.33

Publications

1 publications found

Variant links:

Genes affected

RSU1 (HGNC:10464): (Ras suppressor protein 1) This gene encodes a protein that is involved in the Ras signal transduction pathway, growth inhibition, and nerve-growth factor induced differentiation processes, as determined in mouse and human cell line studies. In mouse, the encoded protein was initially isolated based on its ability to inhibit v-Ras transformation. Multiple alternatively spliced transcript variants for this gene have been reported; one of these variants was found only in glioma tumors. [provided by RefSeq, Jul 2008]

RSU1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012425.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSU1	NM_012425.4	MANE Select	c.599-4_599-3dupCC		splice_region intron	N/A	NP_036557.1	Q15404-1
	RSU1	NM_152724.3		c.440-4_440-3dupCC		splice_region intron	N/A	NP_689937.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RSU1	ENST00000345264.10	TSL:1 MANE Select	c.599-3_599-2insCC	splice_region intron	N/A	ENSP00000339521.5	Q15404-1
RSU1	ENST00000377921.7	TSL:1	c.599-3_599-2insCC	splice_region intron	N/A	ENSP00000367154.3	Q15404-1
RSU1	ENST00000602389.1	TSL:1	c.440-3_440-2insCC	splice_region intron	N/A	ENSP00000473588.1	Q15404-2

Frequencies

GnomAD3 genomes

AF:

0.00198

AC:

254

AN:

128100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000921

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0127

Gnomad SAS

AF:

0.00932

Gnomad FIN

AF:

0.00161

Gnomad MID

AF:

0.00352

Gnomad NFE

AF:

0.00143

Gnomad OTH

AF:

0.00116

GnomAD4 exome

AF:

0.000889

AC:

954

AN:

1073620

Hom.:

Cov.:

AF XY:

0.000949

AC XY:

506

AN XY:

533348

show subpopulations

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

African (AFR)

AF:

0.000783

AC:

AN:

25546

American (AMR)

AF:

0.000688

AC:

AN:

27636

Ashkenazi Jewish (ASJ)

AF:

0.000167

AC:

AN:

17970

East Asian (EAS)

AF:

0.00274

AC:

AN:

28468

South Asian (SAS)

AF:

0.00307

AC:

186

AN:

60494

European-Finnish (FIN)

AF:

0.00126

AC:

AN:

35760

Middle Eastern (MID)

AF:

0.000461

AC:

AN:

4334

European-Non Finnish (NFE)

AF:

0.000647

AC:

537

AN:

829636

Other (OTH)

AF:

0.00146

AC:

AN:

43776

⚠️ 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: 0.290

Heterozygous variant carriers

165

247

330

412

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.00198

AC:

254

AN:

128164

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

131

AN XY:

61100

show subpopulations

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

African (AFR)

AF:

0.00165

AC:

AN:

34600

American (AMR)

AF:

0.000920

AC:

AN:

13048

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3140

East Asian (EAS)

AF:

0.0123

AC:

AN:

4234

South Asian (SAS)

AF:

0.00939

AC:

AN:

3514

European-Finnish (FIN)

AF:

0.00161

AC:

AN:

6822

Middle Eastern (MID)

AF:

0.00379

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.00143

AC:

AN:

60052

Other (OTH)

AF:

0.00114

AC:

AN:

1750

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.371

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:

0.00164

Hom.:

109

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.3

Mutation Taster

=93/7

polymorphism

(source)

Splicing

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