Genetic Variant MRAS:c.*1011C>T (chr3-138403280-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001085049.3(MRAS):c.*1011C>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 0.121 in 152,140 control chromosomes in the GnomAD database, including 1,203 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1203 hom., cov: 32)

Exomes 𝑓: 0.083 ( 0 hom. )

Consequence

MRAS
NM_001085049.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0330

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 3-138403280-C-T is Benign according to our data. Variant chr3-138403280-C-T is described in ClinVar as [Benign]. Clinvar id is 1650099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.*1011C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000423968.7	NP_001078518.1	O14807-1Q6FGP0Q8WVM9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRAS	ENST00000423968.7 link	c.*1011C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_001085049.3	ENSP00000389682.2		O14807-1

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

18459

AN:

152010

Hom.:

1201

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0932

Gnomad AMI

AF:

0.194

Gnomad AMR

AF:

0.0892

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.0249

Gnomad SAS

AF:

0.0838

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.112

GnomAD4 exome

AF:

0.0833

AC:

AN:

Hom.:

Cov.:

AF XY:

0.100

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.167

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.121

AC:

18477

AN:

152128

Hom.:

1203

Cov.:

AF XY:

0.116

AC XY:

8607

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0932

Gnomad4 AMR

AF:

0.0890

Gnomad4 ASJ

AF:

0.144

Gnomad4 EAS

AF:

0.0249

Gnomad4 SAS

AF:

0.0833

Gnomad4 FIN

AF:

0.105

Gnomad4 NFE

AF:

0.157

Gnomad4 OTH

AF:

0.116

Alfa

AF:

0.138

Hom.:

2956

Bravo

AF:

0.116

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.7

DANN

Benign

0.67

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