3-138372859-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001085049.3(MRAS):c.-18-7G>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 1,498,120 control chromosomes in the GnomAD database, including 506,588 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.85 (54742 hom., cov: 33)
  • Exomes 𝑓: 0.82 (451846 hom.)
• Consequence: MRAS NM_001085049.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002097
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.533

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 3-138372859-G-T is Benign according to our data. Variant chr3-138372859-G-T is described in ClinVar as [Benign]. Clinvar id is 1221389.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRAS	NM_001085049.3	c.-18-7G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000423968.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRAS	ENST00000423968.7	c.-18-7G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001085049.3	P1

Frequencies

GnomAD3 genomes AF: 0.846 AC: 128693 AN: 152062 Hom.: 54679 Cov.: 33

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.832

GnomAD3 exomes AF: 0.824 AC: 135896 AN: 164858 Hom.: 56372 AF XY: 0.816 AC XY: 74824 AN XY: 91700

Gnomad AFR exome AF: 0.906

Gnomad AMR exome AF: 0.910

Gnomad ASJ exome AF: 0.785

Gnomad EAS exome AF: 0.969

Gnomad SAS exome AF: 0.790

Gnomad FIN exome AF: 0.785

Gnomad NFE exome AF: 0.807

Gnomad OTH exome AF: 0.816

GnomAD4 exome AF: 0.818 AC: 1101480 AN: 1345940 Hom.: 451846 Cov.: 32 AF XY: 0.817 AC XY: 543841 AN XY: 665910

Gnomad4 AFR exome AF: 0.909

Gnomad4 AMR exome AF: 0.898

Gnomad4 ASJ exome AF: 0.788

Gnomad4 EAS exome AF: 0.965

Gnomad4 SAS exome AF: 0.788

Gnomad4 FIN exome AF: 0.786

Gnomad4 NFE exome AF: 0.815

Gnomad4 OTH exome AF: 0.818

GnomAD4 genome AF: 0.846 AC: 128815 AN: 152180 Hom.: 54742 Cov.: 33 AF XY: 0.846 AC XY: 62969 AN XY: 74388

Gnomad4 AFR AF: 0.907

Gnomad4 AMR AF: 0.870

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.974

Gnomad4 SAS AF: 0.788

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.811

Gnomad4 OTH AF: 0.834

Alfa AF: 0.814 Hom.: 69659

Bravo AF: 0.855

Asia WGS AF: 0.891 AC: 3101 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.8
Dann	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000021
dbscSNV1_RF	Benign	0.012
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

Other links and lift over

dbSNP: rs1199333; hg19: chr3-138091701;