Variant 5-87267937-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002890.3(RASA1):c.-515C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 367,460 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.012 ( 11 hom., cov: 31)

Exomes 𝑓: 0.015 ( 51 hom. )

Consequence

RASA1
NM_002890.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.15

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 5-87267937-C-T is Benign according to our data. Variant chr5-87267937-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1219209.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0124 (1840/148750) while in subpopulation NFE AF= 0.0181 (1211/66968). AF 95% confidence interval is 0.0172. There are 11 homozygotes in gnomad4. There are 895 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1840 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASA1	NM_002890.3 linkuse as main transcript	c.-515C>T		5_prime_UTR_variant	1/25	ENST00000274376.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASA1	ENST00000274376.11 linkuse as main transcript	c.-515C>T		5_prime_UTR_variant	1/25	1	NM_002890.3	P2	P20936-1
RASA1	ENST00000515800.6 linkuse as main transcript	c.-515C>T		5_prime_UTR_variant, NMD_transcript_variant	1/26	1			P20936-3

Frequencies

GnomAD3 genomes

AF:

0.0124

AC:

1839

AN:

148634

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00265

Gnomad AMI

AF:

0.0310

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.000877

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00366

Gnomad FIN

AF:

0.0272

Gnomad MID

AF:

0.00667

Gnomad NFE

AF:

0.0181

Gnomad OTH

AF:

0.00938

GnomAD4 exome

AF:

0.0151

AC:

3313

AN:

218710

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

1693

AN XY:

111768

show subpopulations

Gnomad4 AFR exome

AF:

0.00435

Gnomad4 AMR exome

AF:

0.0106

Gnomad4 ASJ exome

AF:

0.00122

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00205

Gnomad4 FIN exome

AF:

0.0310

Gnomad4 NFE exome

AF:

0.0174

Gnomad4 OTH exome

AF:

0.0133

GnomAD4 genome

AF:

0.0124

AC:

1840

AN:

148750

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

895

AN XY:

72564

show subpopulations

Gnomad4 AFR

AF:

0.00265

Gnomad4 AMR

AF:

0.0113

Gnomad4 ASJ

AF:

0.000877

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00389

Gnomad4 FIN

AF:

0.0272

Gnomad4 NFE

AF:

0.0181

Gnomad4 OTH

AF:

0.00928

Alfa

AF:

0.0139

Hom.:

Bravo

AF:

0.0110

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.79

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over