rs2347252

Variant names:

• chr3-138376683-T-C
• rs2347252
• NM_001085049.3:c.193+3607T>C

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+3607T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,214 control chromosomes in the GnomAD database, including 1,424 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 0.13 (1424 hom., cov: 33)
• Consequence: MRAS NM_001085049.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• Publications: 20 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRAS	NM_001085049.3	MANE Select	c.193+3607T>C		intron	N/A	NP_001078518.1
	MRAS	NM_001252090.2		c.193+3607T>C		intron	N/A	NP_001239019.1
	MRAS	NM_012219.4		c.193+3607T>C		intron	N/A	NP_036351.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRAS	ENST00000423968.7	TSL:1 MANE Select	c.193+3607T>C		intron	N/A	ENSP00000389682.2
	MRAS	ENST00000289104.8	TSL:2	c.193+3607T>C		intron	N/A	ENSP00000289104.4
	MRAS	ENST00000474559.1	TSL:3	c.193+3607T>C		intron	N/A	ENSP00000418356.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20301 AN: 152096 Hom.: 1424 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.0946

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0254

Gnomad SAS AF: 0.0841

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.133 AC: 20317 AN: 152214 Hom.: 1424 Cov.: 33 AF XY: 0.127 AC XY: 9482 AN XY: 74426

African (AFR) AF: 0.129 AC: 5364 AN: 41520

American (AMR) AF: 0.0944 AC: 1444 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 503 AN: 3472

East Asian (EAS) AF: 0.0254 AC: 132 AN: 5192

South Asian (SAS) AF: 0.0835 AC: 403 AN: 4826

European-Finnish (FIN) AF: 0.106 AC: 1125 AN: 10600

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10880 AN: 67994

Other (OTH) AF: 0.123 AC: 259 AN: 2114

Alfa AF: 0.139 Hom.: 759

Bravo AF: 0.129

Asia WGS AF: 0.0660 AC: 227 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.6
DANN	Benign	0.76
PhyloP100		-0.081
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: rs2347252; hg19: chr3-138095525;