5-87268153-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002890.3(RASA1):c.-299T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.022 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.203

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASA1	NM_002890.3	c.-299T>G		5_prime_UTR_variant	1/25	ENST00000274376.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASA1	ENST00000274376.11	c.-299T>G		5_prime_UTR_variant	1/25	1	NM_002890.3	P2
RASA1	ENST00000515800.6	c.-299T>G		5_prime_UTR_variant, NMD_transcript_variant	1/26	1

Frequencies

GnomAD3 genomes AF: 0.0316 AC: 4815 AN: 152162 Hom.: 156 Cov.: 32

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.: 79 Cov.: 0 AF XY: 0.0166 AC XY: 2422 AN XY: 145770

Gnomad4 AFR exome AF: 0.0759

Gnomad4 AMR exome AF: 0.0142

Gnomad4 ASJ exome AF: 0.0292

Gnomad4 EAS exome AF: 0.0000404

Gnomad4 SAS exome AF: 0.00558

Gnomad4 FIN exome AF: 0.0194

Gnomad4 NFE exome AF: 0.0159

Gnomad4 OTH exome AF: 0.0201

GnomAD4 genome AF: 0.0318 AC: 4840 AN: 152280 Hom.: 162 Cov.: 32 AF XY: 0.0315 AC XY: 2349 AN XY: 74462

Gnomad4 AFR AF: 0.0738

Gnomad4 AMR AF: 0.0149

Gnomad4 ASJ AF: 0.0325

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00850

Gnomad4 FIN AF: 0.0183

Gnomad4 NFE AF: 0.0164

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0222 Hom.: 37

Bravo AF: 0.0327

Asia WGS AF: 0.0180 AC: 61 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

Jul 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	14
Dann	Benign	0.74

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

LitVar

Other links and lift over

dbSNP: rs16876684; hg19: chr5-86563970;