rs7183668

Variant names:

• chr15-78963816-G-T
• rs7183668
• NM_001145648.3:c.3682-1580C>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.3682-1580C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 152,006 control chromosomes in the GnomAD database, including 35,528 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 0.65 (35528 hom., cov: 32)
• Consequence: RASGRF1 NM_001145648.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGRF1	NM_001145648.3	c.3682-1580C>A		intron_variant	Intron 26 of 26	ENST00000558480.7	NP_001139120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGRF1	ENST00000558480.7	c.3682-1580C>A		intron_variant	Intron 26 of 26	2	NM_001145648.3	ENSP00000452781.2
RASGRF1	ENST00000394745.3	c.1378-1580C>A		intron_variant	Intron 13 of 13	1		ENSP00000378228.3
RASGRF1	ENST00000419573.7	c.3730-1580C>A		intron_variant	Intron 27 of 27	2		ENSP00000405963.3

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99155 AN: 151886 Hom.: 35521 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.653 AC: 99184 AN: 152006 Hom.: 35528 Cov.: 32 AF XY: 0.652 AC XY: 48437 AN XY: 74308

African (AFR) AF: 0.383 AC: 15874 AN: 41438

American (AMR) AF: 0.579 AC: 8838 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2594 AN: 3468

East Asian (EAS) AF: 0.316 AC: 1637 AN: 5178

South Asian (SAS) AF: 0.818 AC: 3934 AN: 4812

European-Finnish (FIN) AF: 0.800 AC: 8454 AN: 10574

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.818 AC: 55593 AN: 67962

Other (OTH) AF: 0.650 AC: 1371 AN: 2110

Alfa AF: 0.747 Hom.: 30704

Bravo AF: 0.619

Asia WGS AF: 0.581 AC: 2020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.8
DANN	Benign	0.79
PhyloP100		0.30
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: rs7183668; hg19: chr15-79256158;