rs9818870

Variant names:

• chr3-138403280-C-T
• rs9818870
• NM_001085049.3:c.*1011C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-138403280-C-T
• chr3-138403280-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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 (★★). The gene MRAS is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.12 (1203 hom., cov: 32)
  • Exomes 𝑓: 0.083 (0 hom.)
• Consequence: MRAS NM_001085049.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0330
• Publications: 156 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: 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

ACMG classification

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

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRAS	NM_001085049.3	MANE Select	c.*1011C>T		3_prime_UTR	Exon 6 of 6	NP_001078518.1	O14807-1
	MRAS	NM_001252090.2		c.*1011C>T		3_prime_UTR	Exon 6 of 6	NP_001239019.1	O14807-1
	MRAS	NM_012219.4		c.*1011C>T		3_prime_UTR	Exon 6 of 6	NP_036351.3	O14807-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRAS	ENST00000423968.7	TSL:1 MANE Select	c.*1011C>T		3_prime_UTR	Exon 6 of 6	ENSP00000389682.2	O14807-1
	MRAS	ENST00000949757.1		c.*1011C>T		3_prime_UTR	Exon 7 of 7	ENSP00000619816.1
	MRAS	ENST00000949759.1		c.*1011C>T		3_prime_UTR	Exon 6 of 6	ENSP00000619818.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18459 AN: 152010 Hom.: 1201 Cov.: 32

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: 1 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.100 AC XY: 1 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 1 AN: 6

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.121 AC: 18477 AN: 152128 Hom.: 1203 Cov.: 32 AF XY: 0.116 AC XY: 8607 AN XY: 74384

African (AFR) AF: 0.0932 AC: 3865 AN: 41476

American (AMR) AF: 0.0890 AC: 1361 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 499 AN: 3468

East Asian (EAS) AF: 0.0249 AC: 129 AN: 5178

South Asian (SAS) AF: 0.0833 AC: 402 AN: 4828

European-Finnish (FIN) AF: 0.105 AC: 1108 AN: 10596

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

European-Non Finnish (NFE) AF: 0.157 AC: 10666 AN: 67978

Other (OTH) AF: 0.116 AC: 246 AN: 2112

Alfa AF: 0.138 Hom.: 6336

Bravo AF: 0.116

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.7
DANN	Benign	0.67
PhyloP100		-0.033
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: rs9818870; hg19: chr3-138122122;