chr5-81207084-T-C

Variant names:

• chr5-81207084-T-C
• rs17228156
• NM_006909.3:c.2968-162T>C

Variant summary

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

The NM_006909.3(RASGRF2):​c.2968-162T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.054 in 152,332 control chromosomes in the GnomAD database, including 278 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 0.054 (278 hom., cov: 33)
• Consequence: RASGRF2 NM_006909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570
• Publications: 5 publications found

Genes affected

RASGRF2 (HGNC:9876): (Ras protein specific guanine nucleotide releasing factor 2) RAS GTPases cycle between an inactive GDP-bound state and an active GTP-bound state. This gene encodes a calcium-regulated nucleotide exchange factor activating both RAS and RAS-related protein, RAC1, through the exchange of bound GDP for GTP, thereby, coordinating the signaling of distinct mitogen-activated protein kinase pathways. [provided by RefSeq, Oct 2011]

LOC124901017 (HGNC:):

CKMT2-AS1 (HGNC:48997): (CKMT2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0698 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006909.3. 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
	RASGRF2	NM_006909.3	MANE Select	c.2968-162T>C		intron	N/A	NP_008840.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGRF2	ENST00000265080.9	TSL:1 MANE Select	c.2968-162T>C		intron	N/A	ENSP00000265080.4
	RASGRF2	ENST00000503795.1	TSL:1	n.2968-162T>C		intron	N/A	ENSP00000421771.1
	CKMT2-AS1	ENST00000503483.6	TSL:3	n.333-2761A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0541 AC: 8232 AN: 152214 Hom.: 277 Cov.: 33

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0670

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.0113

Gnomad SAS AF: 0.0767

Gnomad FIN AF: 0.0478

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0707

Gnomad OTH AF: 0.0669

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

GnomAD4 genome AF: 0.0540 AC: 8224 AN: 152332 Hom.: 278 Cov.: 33 AF XY: 0.0534 AC XY: 3976 AN XY: 74494

African (AFR) AF: 0.0213 AC: 886 AN: 41580

American (AMR) AF: 0.0669 AC: 1023 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0974 AC: 338 AN: 3472

East Asian (EAS) AF: 0.0114 AC: 59 AN: 5194

South Asian (SAS) AF: 0.0762 AC: 368 AN: 4830

European-Finnish (FIN) AF: 0.0478 AC: 508 AN: 10624

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0707 AC: 4806 AN: 68014

Other (OTH) AF: 0.0666 AC: 141 AN: 2116

Alfa AF: 0.0675 Hom.: 298

Bravo AF: 0.0531

Asia WGS AF: 0.0350 AC: 120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.66
PhyloP100		0.057
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: rs17228156; hg19: chr5-80502903;