chr15-78981704-C-T

Variant names:

• chr15-78981704-C-T
• rs3743200
• NM_001145648.3:c.3415-1005G>A

Variant summary

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

The NM_001145648.3(RASGRF1):​c.3415-1005G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,214 control chromosomes in the GnomAD database, including 4,361 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 0.24 (4361 hom., cov: 33)
  • Exomes 𝑓: 0.21 (0 hom.)
• Consequence: RASGRF1 NM_001145648.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 19 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145648.3. 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
	RASGRF1	NM_001145648.3	MANE Select	c.3415-1005G>A		intron	N/A	NP_001139120.1
	RASGRF1	NM_002891.6		c.3463-1005G>A		intron	N/A	NP_002882.3
	RASGRF1	NM_153815.3		c.1111-1005G>A		intron	N/A	NP_722522.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGRF1	ENST00000558480.7	TSL:2 MANE Select	c.3415-1005G>A		intron	N/A	ENSP00000452781.2
	RASGRF1	ENST00000394745.3	TSL:1	c.1111-1005G>A		intron	N/A	ENSP00000378228.3
	RASGRF1	ENST00000560334.5	TSL:1	n.3285-1005G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35999 AN: 152038 Hom.: 4358 Cov.: 33

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.207 AC: 12 AN: 58 Hom.: 0 Cov.: 0 AF XY: 0.222 AC XY: 8 AN XY: 36

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.222 AC: 12 AN: 54

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.237 AC: 36024 AN: 152156 Hom.: 4361 Cov.: 33 AF XY: 0.235 AC XY: 17444 AN XY: 74376

African (AFR) AF: 0.232 AC: 9633 AN: 41506

American (AMR) AF: 0.192 AC: 2945 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 734 AN: 3470

East Asian (EAS) AF: 0.189 AC: 980 AN: 5184

South Asian (SAS) AF: 0.227 AC: 1094 AN: 4816

European-Finnish (FIN) AF: 0.267 AC: 2822 AN: 10572

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.251 AC: 17067 AN: 67994

Other (OTH) AF: 0.232 AC: 489 AN: 2112

Alfa AF: 0.244 Hom.: 15157

Bravo AF: 0.234

Asia WGS AF: 0.213 AC: 742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.86
DANN	Benign	0.60
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3743200; hg19: chr15-79274046;