rs2347252

chr3-138376683-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRAS	NM_001085049.3	c.193+3607T>C		intron_variant		ENST00000423968.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRAS	ENST00000423968.7	c.193+3607T>C		intron_variant		1	NM_001085049.3	P1

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

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.0944

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.0254

Gnomad4 SAS AF: 0.0835

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.123

Alfa AF: 0.137 Hom.: 479

Bravo AF: 0.129

Asia WGS AF: 0.0660 AC: 227 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	5.6
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs2347252; hg19: chr3-138095525;