3-138381697-T-G

Variant names:

• chr3-138381697-T-G
• rs1720819
• NM_001085049.3:c.193+8621T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001085049.3(MRAS):​c.193+8621T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,170 control chromosomes in the GnomAD database, including 3,249 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 0.18 (3249 hom., cov: 32)
• Consequence: MRAS NM_001085049.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257
• Publications: 7 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRAS	NM_001085049.3	c.193+8621T>G		intron_variant	Intron 2 of 5	ENST00000423968.7	NP_001078518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRAS	ENST00000423968.7	c.193+8621T>G		intron_variant	Intron 2 of 5	1	NM_001085049.3	ENSP00000389682.2

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27364 AN: 152052 Hom.: 3242 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0953

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.0914

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.180 AC: 27398 AN: 152170 Hom.: 3249 Cov.: 32 AF XY: 0.176 AC XY: 13112 AN XY: 74404

African (AFR) AF: 0.341 AC: 14131 AN: 41488

American (AMR) AF: 0.0952 AC: 1455 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 433 AN: 3470

East Asian (EAS) AF: 0.242 AC: 1251 AN: 5170

South Asian (SAS) AF: 0.0905 AC: 437 AN: 4830

European-Finnish (FIN) AF: 0.115 AC: 1222 AN: 10608

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7986 AN: 68002

Other (OTH) AF: 0.158 AC: 333 AN: 2108

Alfa AF: 0.127 Hom.: 949

Bravo AF: 0.184

Asia WGS AF: 0.155 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.9
DANN	Benign	0.66
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1720819; hg19: chr3-138100539;