rs2306374

chr3-138401110-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.527+497T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,282 control chromosomes in the GnomAD database, including 1,164 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 0.12 (1164 hom., cov: 32)
• Consequence: MRAS NM_001085049.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341

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=-0.69).
• 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.527+497T>C		intron_variant		ENST00000423968.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRAS	ENST00000423968.7	c.527+497T>C		intron_variant		1	NM_001085049.3	P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17694 AN: 152164 Hom.: 1163 Cov.: 32

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.0875

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0248

Gnomad SAS AF: 0.0836

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.116 AC: 17706 AN: 152282 Hom.: 1164 Cov.: 32 AF XY: 0.111 AC XY: 8239 AN XY: 74456

Gnomad4 AFR AF: 0.0697

Gnomad4 AMR AF: 0.0874

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.0249

Gnomad4 SAS AF: 0.0831

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.114

Alfa AF: 0.145 Hom.: 3731

Bravo AF: 0.109

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	6.8
Dann	Benign	0.87

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: rs2306374; hg19: chr3-138119952;