chr3-138403078-A-T

Variant names:

• chr3-138403078-A-T
• rs3732837
• NM_001085049.3:c.*809A>T

Variant summary

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

The NM_001085049.3(MRAS):​c.*809A>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 0.115 in 152,262 control chromosomes in the GnomAD database, including 1,122 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 0.11 (1122 hom., cov: 32)
  • Exomes 𝑓: 0.19 (0 hom.)
• Consequence: MRAS NM_001085049.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644
• 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=-0.81).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRAS	NM_001085049.3	MANE Select	c.*809A>T		3_prime_UTR	Exon 6 of 6	NP_001078518.1
	MRAS	NM_001252090.2		c.*809A>T		3_prime_UTR	Exon 6 of 6	NP_001239019.1
	MRAS	NM_012219.4		c.*809A>T		3_prime_UTR	Exon 6 of 6	NP_036351.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRAS	ENST00000423968.7	TSL:1 MANE Select	c.*809A>T		3_prime_UTR	Exon 6 of 6	ENSP00000389682.2
	MRAS	ENST00000289104.8	TSL:2	c.*809A>T		3_prime_UTR	Exon 6 of 6	ENSP00000289104.4
	MRAS	ENST00000464896.5	TSL:2	c.*809A>T		3_prime_UTR	Exon 5 of 5	ENSP00000419582.1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17440 AN: 152128 Hom.: 1121 Cov.: 32

Gnomad AFR AF: 0.0692

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.0874

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.0249

Gnomad SAS AF: 0.0837

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.188 AC: 3 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

African (AFR) AF: 0.00 AC: 0 AN: 2

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: 0.300 AC: 3 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

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

GnomAD4 genome AF: 0.115 AC: 17452 AN: 152246 Hom.: 1122 Cov.: 32 AF XY: 0.109 AC XY: 8140 AN XY: 74450

African (AFR) AF: 0.0691 AC: 2872 AN: 41566

American (AMR) AF: 0.0873 AC: 1336 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 500 AN: 3472

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

South Asian (SAS) AF: 0.0831 AC: 401 AN: 4824

European-Finnish (FIN) AF: 0.104 AC: 1102 AN: 10604

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

European-Non Finnish (NFE) AF: 0.157 AC: 10672 AN: 67986

Other (OTH) AF: 0.113 AC: 239 AN: 2112

Alfa AF: 0.0455 Hom.: 53

Bravo AF: 0.108

Asia WGS AF: 0.0630 AC: 217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.75
DANN	Benign	0.83
PhyloP100		-0.64
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: rs3732837; hg19: chr3-138121920;