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1-231626909-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_018662.3(DISC1):c.42C>T(p.Gly14=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00058 in 1,502,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00060 ( 0 hom. )

Consequence

DISC1
NM_018662.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.715
Variant links:
Genes affected
DISC1 (HGNC:2888): (DISC1 scaffold protein) This gene encodes a protein with multiple coiled coil motifs which is located in the nucleus, cytoplasm and mitochondria. The protein is involved in neurite outgrowth and cortical development through its interaction with other proteins. This gene is disrupted in a t(1;11)(q42.1;q14.3) translocation which segregates with schizophrenia and related psychiatric disorders in a large Scottish family. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
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=-0.59).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-231626909-C-T is Benign according to our data. Variant chr1-231626909-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3049350.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=-0.715 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DISC1NM_018662.3 linkuse as main transcriptc.42C>T p.Gly14= synonymous_variant 1/13 ENST00000439617.8
TSNAX-DISC1NR_028393.1 linkuse as main transcriptn.788+10003C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DISC1ENST00000439617.8 linkuse as main transcriptc.42C>T p.Gly14= synonymous_variant 1/135 NM_018662.3 A2Q9NRI5-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000396
AC:
60
AN:
151646
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000194
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000655
Gnomad ASJ
AF:
0.000577
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000531
Gnomad OTH
AF:
0.00192
GnomAD3 exomes
AF:
0.000350
AC:
35
AN:
99984
Hom.:
0
AF XY:
0.000284
AC XY:
16
AN XY:
56350
show subpopulations
Gnomad AFR exome
AF:
0.000975
Gnomad AMR exome
AF:
0.000320
Gnomad ASJ exome
AF:
0.000875
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000199
Gnomad NFE exome
AF:
0.000446
Gnomad OTH exome
AF:
0.000978
GnomAD4 exome
AF:
0.000601
AC:
812
AN:
1350532
Hom.:
0
Cov.:
30
AF XY:
0.000623
AC XY:
415
AN XY:
666578
show subpopulations
Gnomad4 AFR exome
AF:
0.000109
Gnomad4 AMR exome
AF:
0.000559
Gnomad4 ASJ exome
AF:
0.000670
Gnomad4 EAS exome
AF:
0.0000304
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000121
Gnomad4 NFE exome
AF:
0.000682
Gnomad4 OTH exome
AF:
0.000784
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000395
AC:
60
AN:
151754
Hom.:
0
Cov.:
31
AF XY:
0.000418
AC XY:
31
AN XY:
74170
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.000655
Gnomad4 ASJ
AF:
0.000577
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000531
Gnomad4 OTH
AF:
0.00190
Alfa
AF:
0.000368
Hom.:
0
Bravo
AF:
0.000476

ClinVar

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

Submissions by phenotype

DISC1-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJan 04, 2021This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
Cadd
Benign
6.0
Dann
Benign
0.89
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.5

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: rs566458514; hg19: chr1-231762655; API