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GeneBe

12-64065207-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_020762.4(SRGAP1):c.1113C>T(p.Ile371=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000546 in 1,612,792 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00029 ( 2 hom. )

Consequence

SRGAP1
NM_020762.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.776
Variant links:
Genes affected
SRGAP1 (HGNC:17382): (SLIT-ROBO Rho GTPase activating protein 1) The protein encoded by this gene is a GTPase activator, working with the GTPase CDC42 to negatively regulate neuronal migration. The encoded protein interacts with the transmembrane receptor ROBO1 to inactivate CDC42. [provided by RefSeq, Sep 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.25).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-64065207-C-T is Benign according to our data. Variant chr12-64065207-C-T is described in ClinVar as [Benign]. Clinvar id is 710135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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=-0.776 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 Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRGAP1NM_020762.4 linkuse as main transcriptc.1113C>T p.Ile371= synonymous_variant 8/22 ENST00000355086.8
SRGAP1NM_001346201.2 linkuse as main transcriptc.1113C>T p.Ile371= synonymous_variant 8/22
SRGAP1XM_024449096.2 linkuse as main transcriptc.1113C>T p.Ile371= synonymous_variant 8/14
SRGAP1XM_024449097.2 linkuse as main transcriptc.1113C>T p.Ile371= synonymous_variant 8/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRGAP1ENST00000355086.8 linkuse as main transcriptc.1113C>T p.Ile371= synonymous_variant 8/221 NM_020762.4 A1Q7Z6B7-1
ENST00000535594.1 linkuse as main transcriptn.134-22267G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00302
AC:
459
AN:
152092
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0101
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00197
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00478
GnomAD3 exomes
AF:
0.000687
AC:
171
AN:
248800
Hom.:
0
AF XY:
0.000483
AC XY:
65
AN XY:
134460
show subpopulations
Gnomad AFR exome
AF:
0.00937
Gnomad AMR exome
AF:
0.000437
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000550
Gnomad SAS exome
AF:
0.0000330
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000889
Gnomad OTH exome
AF:
0.000330
GnomAD4 exome
AF:
0.000287
AC:
419
AN:
1460582
Hom.:
2
Cov.:
30
AF XY:
0.000249
AC XY:
181
AN XY:
726558
show subpopulations
Gnomad4 AFR exome
AF:
0.0108
Gnomad4 AMR exome
AF:
0.000471
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.000514
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00304
AC:
462
AN:
152210
Hom.:
3
Cov.:
32
AF XY:
0.00290
AC XY:
216
AN XY:
74432
show subpopulations
Gnomad4 AFR
AF:
0.0101
Gnomad4 AMR
AF:
0.00196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.00147
Hom.:
0
Bravo
AF:
0.00342

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

SRGAP1-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJul 24, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
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
-0.25
Cadd
Benign
6.9
Dann
Benign
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs112908570; hg19: chr12-64458987; API