dbSNP rs1678443: MRAS:c.193+5616C>A (chr3-138378692-C-A) – 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.193+5616C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0844 in 152,200 control chromosomes in the GnomAD database, including 1,396 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. The gene MRAS is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.084 ( 1396 hom., cov: 32)

Consequence

MRAS
NM_001085049.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.812

Publications

6 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
Noonan syndrome
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet
cardiofaciocutaneous syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Costello syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Noonan syndrome with multiple lentigines
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Noonan syndrome-like disorder with loose anagen hair
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

MRAS links:

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ACMG classification

Specifications for MRAS are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085049.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MRAS	NM_001085049.3	MANE Select	c.193+5616C>A	intron	N/A	NP_001078518.1	O14807-1
MRAS	NM_001252090.2		c.193+5616C>A	intron	N/A	NP_001239019.1	O14807-1
MRAS	NM_012219.4		c.193+5616C>A	intron	N/A	NP_036351.3	O14807-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MRAS	ENST00000423968.7	TSL:1 MANE Select	c.193+5616C>A	intron	N/A	ENSP00000389682.2	O14807-1
MRAS	ENST00000949757.1		c.193+5616C>A	intron	N/A	ENSP00000619816.1
MRAS	ENST00000949759.1		c.193+5616C>A	intron	N/A	ENSP00000619818.1

Frequencies

GnomAD3 genomes

AF:

0.0843

AC:

12822

AN:

152082

Hom.:

1395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0291

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.0157

Gnomad FIN

AF:

0.0440

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00245

Gnomad OTH

AF:

0.0660

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0844

AC:

12841

AN:

152200

Hom.:

1396

Cov.:

AF XY:

0.0849

AC XY:

6320

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.251

AC:

10393

AN:

41472

American (AMR)

AF:

0.0291

AC:

445

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00893

AC:

AN:

3472

East Asian (EAS)

AF:

0.216

AC:

1117

AN:

5174

South Asian (SAS)

AF:

0.0153

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0440

AC:

467

AN:

10616

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00246

AC:

167

AN:

68022

Other (OTH)

AF:

0.0649

AC:

137

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

508

1016

1523

2031

2539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<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:

0.0834

Hom.:

696

Bravo

AF:

0.0926

Asia WGS

AF:

0.0980

AC:

341

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.3

(source)

DANN

Benign

0.61

PhyloP100

0.81

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over