Variant chr19-49635861-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_006270.5(RRAS):c.454-9T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RRAS
NM_006270.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00005769

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.252

Variant links:

Genes affected

RRAS (HGNC:10447): (RAS related) The protein encoded by this gene is a small GTPase involved in diverse processes including angiogenesis, vascular homeostasis and regeneration, cell adhesion, and neuronal axon guidance. Mutations in this gene are found in many invasive cancers. [provided by RefSeq, Jul 2015]

RRAS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 19-49635861-A-G is Benign according to our data. Variant chr19-49635861-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 457989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RRAS	NM_006270.5 linkuse as main transcript	c.454-9T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000246792.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RRAS	ENST00000246792.4 linkuse as main transcript	c.454-9T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_006270.5	P1
RRAS	ENST00000601532.1 linkuse as main transcript	n.594-9T>C		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

94644

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000112

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00107

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000488

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000866

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000271

AC:

AN:

147664

Hom.:

AF XY:

0.000277

AC XY:

AN XY:

82972

show subpopulations

Gnomad AFR exome

AF:

0.000107

Gnomad AMR exome

AF:

0.000595

Gnomad ASJ exome

AF:

0.000619

Gnomad EAS exome

AF:

0.000442

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.000194

Gnomad OTH exome

AF:

0.000294

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00152

AC:

497

AN:

326264

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

263

AN XY:

178060

show subpopulations

Gnomad4 AFR exome

AF:

0.00163

Gnomad4 AMR exome

AF:

0.00329

Gnomad4 ASJ exome

AF:

0.00179

Gnomad4 EAS exome

AF:

0.000843

Gnomad4 SAS exome

AF:

0.00183

Gnomad4 FIN exome

AF:

0.00180

Gnomad4 NFE exome

AF:

0.00126

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000180

AC:

AN:

94690

Hom.:

Cov.:

AF XY:

0.000270

AC XY:

AN XY:

44464

show subpopulations

Gnomad4 AFR

AF:

0.000112

Gnomad4 AMR

AF:

0.00107

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000488

Gnomad4 NFE

AF:

0.0000866

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0201

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 28, 2021

- -

Noonan syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 28, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.8

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000058

dbscSNV1_RF

Benign

0.0

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