3-138370671-C-T

Position:

• chr3-138370671-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001085049.3(MRAS):​c.-18-2195C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,012 control chromosomes in the GnomAD database, including 27,610 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 0.59 (27610 hom., cov: 32)
• Consequence: MRAS NM_001085049.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRAS	NM_001085049.3	c.-18-2195C>T		intron_variant		ENST00000423968.7	NP_001078518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRAS	ENST00000423968.7	c.-18-2195C>T		intron_variant		1	NM_001085049.3	ENSP00000389682	P1

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89797 AN: 151894 Hom.: 27598 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.591 AC: 89839 AN: 152012 Hom.: 27610 Cov.: 32 AF XY: 0.598 AC XY: 44424 AN XY: 74326

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.728

Gnomad4 ASJ AF: 0.637

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.626

Alfa AF: 0.613 Hom.: 5505

Bravo AF: 0.592

Asia WGS AF: 0.715 AC: 2489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.28
DANN	Benign	0.66

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: rs4678260; hg19: chr3-138089513;