5-87267958-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002890.3(RASA1):c.-493dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 398,582 control chromosomes in the GnomAD database, including 8,226 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2733 hom., cov: 24)
  • Exomes 𝑓: 0.20 (5493 hom.)
• Consequence: RASA1 NM_002890.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.867

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-87267958-C-CA is Benign according to our data. Variant chr5-87267958-C-CA is described in ClinVar as [Benign]. Clinvar id is 1252411.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASA1	NM_002890.3	c.-493dup		5_prime_UTR_variant	1/25	ENST00000274376.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASA1	ENST00000274376.11	c.-493dup		5_prime_UTR_variant	1/25	1	NM_002890.3	P2
RASA1	ENST00000515800.6	c.-493dup		5_prime_UTR_variant, NMD_transcript_variant	1/26	1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27331 AN: 151128 Hom.: 2740 Cov.: 24

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.200 AC: 49443 AN: 247338 Hom.: 5493 Cov.: 0 AF XY: 0.201 AC XY: 25304 AN XY: 125590

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.134

Gnomad4 ASJ exome AF: 0.209

Gnomad4 EAS exome AF: 0.345

Gnomad4 SAS exome AF: 0.334

Gnomad4 FIN exome AF: 0.128

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.209

GnomAD4 genome AF: 0.181 AC: 27322 AN: 151244 Hom.: 2733 Cov.: 24 AF XY: 0.180 AC XY: 13340 AN XY: 73906

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.185

Alfa AF: 0.0501 Hom.: 46

Asia WGS AF: 0.316 AC: 1102 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2019

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Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs3840522; hg19: chr5-86563775;