rs16876684

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002890.3(RASA1):c.-299T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.022 in 437,668 control chromosomes in the GnomAD database, including 241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.032 ( 162 hom., cov: 32)

Exomes 𝑓: 0.017 ( 79 hom. )

Consequence

RASA1
NM_002890.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.203

Publications

1 publications found

Variant links:

Genes affected

RASA1 (HGNC:9871): (RAS p21 protein activator 1) The protein encoded by this gene is located in the cytoplasm and is part of the GAP1 family of GTPase-activating proteins. The gene product stimulates the GTPase activity of normal RAS p21 but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Mutations also have been associated with hereditary capillary malformations (CM) with or without arteriovenous malformations (AVM) and Parkes Weber syndrome. Alternative splicing results in two isoforms where the shorter isoform, lacking the N-terminal hydrophobic region but retaining the same activity, appears to be abundantly expressed in placental but not adult tissues. [provided by RefSeq, May 2012]

RASA1 Gene-Disease associations (from GenCC):

capillary malformation-arteriovenous malformation 1
Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, G2P
capillary malformation-arteriovenous malformation syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Parkes Weber syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
cardiofaciocutaneous syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Costello syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Noonan syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Noonan syndrome with multiple lentigines
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Noonan syndrome-like disorder with loose anagen hair
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
telangiectasia, hereditary hemorrhagic, type 1
Inheritance: AD Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

RASA1 links:

ENSG00000303897 (HGNC:):

ENSG00000303897 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 5-87268153-T-G is Benign according to our data. Variant chr5-87268153-T-G is described in ClinVar as Benign. ClinVar VariationId is 1279556.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0716 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002890.3. 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
	RASA1	NM_002890.3	MANE Select	c.-299T>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 25	NP_002881.1	P20936-1
	RASA1	NM_002890.3	MANE Select	c.-299T>G		5_prime_UTR	Exon 1 of 25	NP_002881.1	P20936-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RASA1	ENST00000274376.11	TSL:1 MANE Select	c.-299T>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 25	ENSP00000274376.6	P20936-1
RASA1	ENST00000274376.11	TSL:1 MANE Select	c.-299T>G	5_prime_UTR	Exon 1 of 25	ENSP00000274376.6	P20936-1
RASA1	ENST00000515800.6	TSL:1	n.-299T>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 26	ENSP00000423395.2	P20936-3

Frequencies

GnomAD3 genomes

AF:

0.0316

AC:

4815

AN:

152162

Hom.:

156

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0735

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0149

Gnomad ASJ

AF:

0.0325

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00850

Gnomad FIN

AF:

0.0183

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0164

Gnomad OTH

AF:

0.0278

GnomAD4 exome

AF:

0.0167

AC:

4772

AN:

285388

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

2422

AN XY:

145770

show subpopulations

African (AFR)

AF:

0.0759

AC:

579

AN:

7628

American (AMR)

AF:

0.0142

AC:

150

AN:

10588

Ashkenazi Jewish (ASJ)

AF:

0.0292

AC:

286

AN:

9782

East Asian (EAS)

AF:

0.0000404

AC:

AN:

24776

South Asian (SAS)

AF:

0.00558

AC:

AN:

10042

European-Finnish (FIN)

AF:

0.0194

AC:

438

AN:

22558

Middle Eastern (MID)

AF:

0.0135

AC:

AN:

1408

European-Non Finnish (NFE)

AF:

0.0159

AC:

2875

AN:

180316

Other (OTH)

AF:

0.0201

AC:

368

AN:

18290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

267

534

800

1067

1334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0318

AC:

4840

AN:

152280

Hom.:

162

Cov.:

AF XY:

0.0315

AC XY:

2349

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0738

AC:

3068

AN:

41560

American (AMR)

AF:

0.0149

AC:

228

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0325

AC:

113

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00850

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0183

AC:

194

AN:

10620

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0164

AC:

1113

AN:

68012

Other (OTH)

AF:

0.0279

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

225

451

676

902

1127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0225

Hom.:

Bravo

AF:

0.0327

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

-0.20

PromoterAI

-0.063

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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