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GeneBe

15-78985067-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001145648.3(RASGRF1):c.3354G>A(p.Ser1118=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000496 in 1,614,056 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00034 ( 2 hom. )

Consequence

RASGRF1
NM_001145648.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.51
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-78985067-C-T is Benign according to our data. Variant chr15-78985067-C-T is described in ClinVar as [Benign]. Clinvar id is 778569.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.51 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 298 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RASGRF1NM_001145648.3 linkuse as main transcriptc.3354G>A p.Ser1118= synonymous_variant 23/27 ENST00000558480.7
LOC100129540NR_148998.1 linkuse as main transcriptn.1041C>T non_coding_transcript_exon_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RASGRF1ENST00000558480.7 linkuse as main transcriptc.3354G>A p.Ser1118= synonymous_variant 23/272 NM_001145648.3 P1Q13972-3
ENST00000316148.4 linkuse as main transcriptn.1041C>T non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00196
AC:
298
AN:
152080
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00575
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00236
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.000791
AC:
199
AN:
251490
Hom.:
2
AF XY:
0.000655
AC XY:
89
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.00652
Gnomad AMR exome
AF:
0.00168
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000193
Gnomad OTH exome
AF:
0.00114
GnomAD4 exome
AF:
0.000343
AC:
502
AN:
1461858
Hom.:
2
Cov.:
33
AF XY:
0.000326
AC XY:
237
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00466
Gnomad4 AMR exome
AF:
0.00181
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000173
Gnomad4 OTH exome
AF:
0.000861
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00196
AC:
298
AN:
152198
Hom.:
0
Cov.:
32
AF XY:
0.00179
AC XY:
133
AN XY:
74400
show subpopulations
Gnomad4 AFR
AF:
0.00573
Gnomad4 AMR
AF:
0.00236
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00105
Hom.:
0
Bravo
AF:
0.00240
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
Cadd
Benign
1.3
Dann
Benign
0.84

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs143238097; hg19: chr15-79277409; API