chr15-78985169-A-G

Variant names:

• chr15-78985169-A-G
• rs2230518
• NM_001145648.3:c.3252T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002891.6(RASGRF1):​c.3300T>C​(p.Asn1100Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,611,868 control chromosomes in the GnomAD database, including 62,195 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 0.30 (7355 hom., cov: 32)
  • Exomes 𝑓: 0.27 (54840 hom.)
• Consequence: RASGRF1 NM_002891.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32
• Publications: 16 publications found

Genes affected

RASGRF1 (HGNC:9875): (Ras protein specific guanine nucleotide releasing factor 1) The protein encoded by this gene is a guanine nucleotide exchange factor (GEF) similar to the Saccharomyces cerevisiae CDC25 gene product. Functional analysis has demonstrated that this protein stimulates the dissociation of GDP from RAS protein. The studies of the similar gene in mouse suggested that the Ras-GEF activity of this protein in brain can be activated by Ca2+ influx, muscarinic receptors, and G protein beta-gamma subunit. Mouse studies also indicated that the Ras-GEF signaling pathway mediated by this protein may be important for long-term memory. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Mar 2009]

ENSG00000177699 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-2.32 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002891.6. 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
	RASGRF1	NM_001145648.3	MANE Select	c.3252T>C	p.Asn1084Asn	synonymous	Exon 23 of 27	NP_001139120.1
	RASGRF1	NM_002891.6		c.3300T>C	p.Asn1100Asn	synonymous	Exon 24 of 28	NP_002882.3
	RASGRF1	NM_153815.3		c.948T>C	p.Asn316Asn	synonymous	Exon 10 of 14	NP_722522.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGRF1	ENST00000558480.7	TSL:2 MANE Select	c.3252T>C	p.Asn1084Asn	synonymous	Exon 23 of 27	ENSP00000452781.2
	RASGRF1	ENST00000394745.3	TSL:1	c.948T>C	p.Asn316Asn	synonymous	Exon 10 of 14	ENSP00000378228.3
	RASGRF1	ENST00000560334.5	TSL:1	n.3122T>C		non_coding_transcript_exon	Exon 22 of 24

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45907 AN: 152000 Hom.: 7347 Cov.: 32

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.293

GnomAD2 exomes AF: 0.262 AC: 65769 AN: 251182 AF XY: 0.261

Gnomad AFR exome AF: 0.418

Gnomad AMR exome AF: 0.207

Gnomad ASJ exome AF: 0.238

Gnomad EAS exome AF: 0.179

Gnomad FIN exome AF: 0.275

Gnomad NFE exome AF: 0.276

Gnomad OTH exome AF: 0.269

GnomAD4 exome AF: 0.271 AC: 395562 AN: 1459750 Hom.: 54840 Cov.: 38 AF XY: 0.270 AC XY: 196196 AN XY: 726262

African (AFR) AF: 0.414 AC: 13841 AN: 33422

American (AMR) AF: 0.208 AC: 9285 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 6241 AN: 26128

East Asian (EAS) AF: 0.209 AC: 8278 AN: 39684

South Asian (SAS) AF: 0.236 AC: 20370 AN: 86216

European-Finnish (FIN) AF: 0.274 AC: 14614 AN: 53412

Middle Eastern (MID) AF: 0.280 AC: 1614 AN: 5764

European-Non Finnish (NFE) AF: 0.275 AC: 304900 AN: 1110102

Other (OTH) AF: 0.272 AC: 16419 AN: 60324

GnomAD4 genome AF: 0.302 AC: 45942 AN: 152118 Hom.: 7355 Cov.: 32 AF XY: 0.298 AC XY: 22139 AN XY: 74370

African (AFR) AF: 0.410 AC: 17020 AN: 41502

American (AMR) AF: 0.226 AC: 3446 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 815 AN: 3470

East Asian (EAS) AF: 0.190 AC: 986 AN: 5180

South Asian (SAS) AF: 0.241 AC: 1161 AN: 4814

European-Finnish (FIN) AF: 0.275 AC: 2905 AN: 10564

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18644 AN: 67990

Other (OTH) AF: 0.291 AC: 616 AN: 2116

Alfa AF: 0.278 Hom.: 13692

Bravo AF: 0.306

Asia WGS AF: 0.227 AC: 788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.029
DANN	Benign	0.43
PhyloP100		-2.3
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2230518; hg19: chr15-79277511; COSMIC: COSV60212215; COSMIC: COSV60212215;