rs3743195

Variant names:

• chr15-78973524-G-A
• rs3743195
• NM_001145648.3:c.3495-104C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-78973524-G-A
• chr15-78973524-G-T

Variant summary

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

The NM_001145648.3(RASGRF1):​c.3495-104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 805,412 control chromosomes in the GnomAD database, including 39,393 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 0.28 (6371 hom., cov: 32)
  • Exomes 𝑓: 0.31 (33022 hom.)
• Consequence: RASGRF1 NM_001145648.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.420
• Publications: 7 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGRF1	NM_001145648.3	MANE Select	c.3495-104C>T		intron	N/A	NP_001139120.1
	RASGRF1	NM_002891.6		c.3543-104C>T		intron	N/A	NP_002882.3
	RASGRF1	NM_153815.3		c.1191-104C>T		intron	N/A	NP_722522.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGRF1	ENST00000558480.7	TSL:2 MANE Select	c.3495-104C>T		intron	N/A	ENSP00000452781.2
	RASGRF1	ENST00000394745.3	TSL:1	c.1191-104C>T		intron	N/A	ENSP00000378228.3
	RASGRF1	ENST00000419573.7	TSL:2	c.3543-104C>T		intron	N/A	ENSP00000405963.3

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42008 AN: 151888 Hom.: 6371 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.312 AC: 203539 AN: 653406 Hom.: 33022 AF XY: 0.309 AC XY: 105816 AN XY: 342328

African (AFR) AF: 0.166 AC: 2737 AN: 16484

American (AMR) AF: 0.317 AC: 8997 AN: 28404

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 4447 AN: 15794

East Asian (EAS) AF: 0.170 AC: 5789 AN: 34104

South Asian (SAS) AF: 0.250 AC: 14063 AN: 56200

European-Finnish (FIN) AF: 0.341 AC: 15733 AN: 46082

Middle Eastern (MID) AF: 0.283 AC: 1117 AN: 3950

European-Non Finnish (NFE) AF: 0.335 AC: 140645 AN: 419806

Other (OTH) AF: 0.307 AC: 10011 AN: 32582

GnomAD4 genome AF: 0.276 AC: 42011 AN: 152006 Hom.: 6371 Cov.: 32 AF XY: 0.273 AC XY: 20286 AN XY: 74292

African (AFR) AF: 0.168 AC: 6978 AN: 41464

American (AMR) AF: 0.295 AC: 4508 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 968 AN: 3468

East Asian (EAS) AF: 0.157 AC: 811 AN: 5160

South Asian (SAS) AF: 0.253 AC: 1215 AN: 4810

European-Finnish (FIN) AF: 0.344 AC: 3632 AN: 10558

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23021 AN: 67954

Other (OTH) AF: 0.275 AC: 581 AN: 2114

Alfa AF: 0.316 Hom.: 9503

Bravo AF: 0.271

Asia WGS AF: 0.193 AC: 673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.86
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3743195; hg19: chr15-79265866;