dbSNP rs16854954: DISC1:c.1634+5776T>C (chr1-231776846-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018662.3(DISC1):c.1634+5776T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,088 control chromosomes in the GnomAD database, including 7,737 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 0.31 ( 7737 hom., cov: 32)

Consequence

DISC1
NM_018662.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.37

Publications

7 publications found

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]

DISC1 links:

TSNAX-DISC1 (HGNC:49177): (TSNAX-DISC1 readthrough (NMD candidate)) This gene represents naturally occurring read-through transcription between the neighboring TSNAX (translin-associated factor X) and DISC1 (disrupted in schizophrenia 1) genes on chromosome 1. Alternative splicing results in multiple transcript variants, all of which are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to be protein-coding. These alterations in gene processing may be associated with risk for psychiatric illness, most notably, schizophrenia. [provided by RefSeq, Nov 2010]

TSNAX-DISC1 links:

ENSG00000286071 (HGNC:):

ENSG00000286071 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.04).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3 link	c.1634+5776T>C		intron_variant	Intron 6 of 12	ENST00000439617.8	NP_061132.2	Q9NRI5-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DISC1	ENST00000439617.8 link	c.1634+5776T>C	intron_variant	Intron 6 of 12	5	NM_018662.3	ENSP00000403888.4	Q9NRI5-1
DISC1	ENST00000366637.8 link	c.1634+5776T>C	intron_variant	Intron 6 of 12	5		ENSP00000355597.6	Q9NRI5-2
TSNAX-DISC1	ENST00000602956.5 link	n.*1495+5776T>C	intron_variant	Intron 10 of 12	2		ENSP00000473532.1	C4P0D8

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46666

AN:

151968

Hom.:

7711

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.354

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.284

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.274

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.302

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

GnomAD4 genome

AF:

0.307

AC:

46739

AN:

152088

Hom.:

7737

Cov.:

AF XY:

0.301

AC XY:

22402

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.423

AC:

17562

AN:

41482

American (AMR)

AF:

0.206

AC:

3152

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

986

AN:

3472

East Asian (EAS)

AF:

0.125

AC:

646

AN:

5176

South Asian (SAS)

AF:

0.192

AC:

928

AN:

4826

European-Finnish (FIN)

AF:

0.265

AC:

2797

AN:

10572

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.289

AC:

19626

AN:

67966

Other (OTH)

AF:

0.301

AC:

636

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1624

3249

4873

6498

8122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.292

Hom.:

11302

Bravo

AF:

0.310

Asia WGS

AF:

0.159

AC:

553

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.050

(source)

DANN

Benign

0.30

PhyloP100

-6.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over