NM_001145648.3:c.276+546T>C

Variant names:

• chr15-79089677-A-G
• rs4778882
• NM_001145648.3:c.276+546T>C

Variant summary

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

The NM_001145648.3(RASGRF1):​c.276+546T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,160 control chromosomes in the GnomAD database, including 22,092 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 0.51 (22092 hom., cov: 33)
• Consequence: RASGRF1 NM_001145648.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGRF1	NM_001145648.3	c.276+546T>C		intron_variant	Intron 1 of 26	ENST00000558480.7	NP_001139120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGRF1	ENST00000558480.7	c.276+546T>C		intron_variant	Intron 1 of 26	2	NM_001145648.3	ENSP00000452781.2
RASGRF1	ENST00000419573.7	c.276+546T>C		intron_variant	Intron 1 of 27	2		ENSP00000405963.3

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77874 AN: 152042 Hom.: 22047 Cov.: 33

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.512 AC: 77981 AN: 152160 Hom.: 22092 Cov.: 33 AF XY: 0.508 AC XY: 37755 AN XY: 74386

African (AFR) AF: 0.765 AC: 31780 AN: 41526

American (AMR) AF: 0.489 AC: 7480 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1248 AN: 3470

East Asian (EAS) AF: 0.505 AC: 2610 AN: 5164

South Asian (SAS) AF: 0.248 AC: 1196 AN: 4828

European-Finnish (FIN) AF: 0.402 AC: 4253 AN: 10590

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28096 AN: 67964

Other (OTH) AF: 0.461 AC: 973 AN: 2110

Alfa AF: 0.458 Hom.: 3097

Bravo AF: 0.541

Asia WGS AF: 0.337 AC: 1171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.9
DANN	Benign	0.14
PhyloP100		-0.042
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: rs4778882; hg19: chr15-79382019;