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rs821616

chr1-232008852-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018662(DISC1):c.2110A>T(p.Ser704Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151696 control chromosomes in the gnomAD Genomes database, including 6428 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.28 ( 6428 hom., cov: 31)
Exomes 𝑓: 0.26 ( 8825 hom. )

Consequence

DISC1
NM_018662 missense

Scores

2
1
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.17

Links

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
?
Computational evidence support a benign effect (MetaRNN=0.0053812265).
BA1
?
GnomAd highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DISC1NM_018662.3 linkuse as main transcriptc.2110A>T p.Ser704Cys missense_variant 11/13 ENST00000439617.8
TSNAX-DISC1NR_028393.1 linkuse as main transcriptn.2776A>T non_coding_transcript_exon_variant 14/16

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DISC1ENST00000439617.8 linkuse as main transcriptc.2110A>T p.Ser704Cys missense_variant 11/135 NM_018662.3 A2Q9NRI5-1

Frequencies

GnomAD3 genomes
AF:
0.285
AC:
43233
AN:
151696
Hom.:
6428
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.332
Gnomad AMI
AF:
0.449
Gnomad AMR
AF:
0.179
Gnomad ASJ
AF:
0.245
Gnomad EAS
AF:
0.121
Gnomad SAS
AF:
0.273
Gnomad FIN
AF:
0.331
Gnomad MID
AF:
0.237
Gnomad NFE
AF:
0.287
Gnomad OTH
AF:
0.251
GnomAD3 exomes
AF:
0.255
AC:
62618
AN:
245122
Hom.:
8825
AF XY:
0.260
AC XY:
34624
AN XY:
133156
show subpopulations
Gnomad AFR exome
AF:
0.343
Gnomad AMR exome
AF:
0.122
Gnomad ASJ exome
AF:
0.243
Gnomad EAS exome
AF:
0.115
Gnomad SAS exome
AF:
0.273
Gnomad FIN exome
AF:
0.331
Gnomad NFE exome
AF:
0.289
Gnomad OTH exome
AF:
0.260
GnomAD4 exome
AF:
0.277
AC:
403925
AN:
1459998
Hom.:
57584
AF XY:
0.278
AC XY:
201633
AN XY:
726138
show subpopulations
Gnomad4 AFR exome
AF:
0.342
Gnomad4 AMR exome
AF:
0.129
Gnomad4 ASJ exome
AF:
0.239
Gnomad4 EAS exome
AF:
0.114
Gnomad4 SAS exome
AF:
0.275
Gnomad4 FIN exome
AF:
0.322
Gnomad4 NFE exome
AF:
0.286
Gnomad4 OTH exome
AF:
0.267
Alfa
AF:
0.277
Hom.:
4534
Bravo
AF:
0.272
TwinsUK
AF:
0.281
AC:
1041
ALSPAC
AF:
0.294
AC:
1132
ESP6500AA
AF:
0.327
AC:
1286
ESP6500EA
AF:
0.286
AC:
2374
ExAC
AF:
0.264
AC:
31900
Asia WGS
AF:
0.217
AC:
754
AN:
3478
EpiCase
AF:
0.281
EpiControl
AF:
0.276

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.70
T
BayesDel_noAF
Benign
-0.51
Cadd
Uncertain
24
Dann
Uncertain
0.98
Eigen
Benign
0.11
Eigen_PC
Benign
0.0093
FATHMM_MKL
Benign
0.65
D
LIST_S2
Benign
0.45
T
MetaRNN
Benign
0.0054
T
MetaSVM
Benign
-0.94
T
MutationTaster
Benign
1.0
P;P;P;P
PROVEAN
Benign
-0.34
N
REVEL
Benign
0.084
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Vest4
0.45
MutPred
0.25
Loss of MoRF binding (P = 0.0132);
ClinPred
0.038
T
GERP RS
2.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

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: rs821616; hg19: chr1-232144598; COSMIC: COSV64093108;