Genetic Variant MRAS:c.*809A>T (chr3-138403078-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001085049.3(MRAS):c.*809A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,262 control chromosomes in the GnomAD database, including 1,122 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 1122 hom., cov: 32)

Exomes 𝑓: 0.19 ( 0 hom. )

Consequence

MRAS
NM_001085049.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.644

Publications

20 publications found

Variant links:

Genes affected

MRAS (HGNC:7227): (muscle RAS oncogene homolog) This gene encodes a member of the Ras family of small GTPases. These membrane-associated proteins function as signal transducers in multiple processes including cell growth and differentiation, and dysregulation of Ras signaling has been associated with many types of cancer. The encoded protein may play a role in the tumor necrosis factor-alpha and MAP kinase signaling pathways. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

MRAS Gene-Disease associations (from GenCC):

Noonan syndrome 11
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
Noonan syndrome
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen

MRAS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRAS	NM_001085049.3 link	c.*809A>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000423968.7	NP_001078518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRAS	ENST00000423968.7 link	c.*809A>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_001085049.3	ENSP00000389682.2

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17440

AN:

152128

Hom.:

1121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0692

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.0874

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.0249

Gnomad SAS

AF:

0.0837

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.109

GnomAD4 exome

AF:

0.188

AC:

AN:

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.300

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.115

AC:

17452

AN:

152246

Hom.:

1122

Cov.:

AF XY:

0.109

AC XY:

8140

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0691

AC:

2872

AN:

41566

American (AMR)

AF:

0.0873

AC:

1336

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

500

AN:

3472

East Asian (EAS)

AF:

0.0249

AC:

129

AN:

5178

South Asian (SAS)

AF:

0.0831

AC:

401

AN:

4824

European-Finnish (FIN)

AF:

0.104

AC:

1102

AN:

10604

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.157

AC:

10672

AN:

67986

Other (OTH)

AF:

0.113

AC:

239

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

816

1631

2447

3262

4078

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<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:

0.0455

Hom.:

Bravo

AF:

0.108

Asia WGS

AF:

0.0630

AC:

217

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.75

(source)

DANN

Benign

0.83

PhyloP100

-0.64

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over