Variant 1-231795302-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_018662.3(DISC1):c.1689+6T>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,609,354 control chromosomes in the GnomAD database, including 13,975 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 0.12 ( 1218 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12757 hom. )

Consequence

DISC1
NM_018662.3 splice_donor_region, intron

Scores

Splicing: ADA: 0.1883

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.50

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3 linkuse as main transcript	c.1689+6T>C		splice_donor_region_variant, intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1 linkuse as main transcript	n.2356-4806T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8 linkuse as main transcript	c.1689+6T>C		splice_donor_region_variant, intron_variant		5	NM_018662.3	A2	Q9NRI5-1
	ENST00000651424.1 linkuse as main transcript	n.259-7959A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18548

AN:

152092

Hom.:

1214

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.0887

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.0671

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.115

GnomAD3 exomes

AF:

0.115

AC:

28597

AN:

247988

Hom.:

1830

AF XY:

0.115

AC XY:

15417

AN XY:

134356

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.0791

Gnomad ASJ exome

AF:

0.117

Gnomad EAS exome

AF:

0.118

Gnomad SAS exome

AF:

0.0650

Gnomad FIN exome

AF:

0.128

Gnomad NFE exome

AF:

0.138

Gnomad OTH exome

AF:

0.106

GnomAD4 exome

AF:

0.130

AC:

188813

AN:

1457146

Hom.:

12757

Cov.:

AF XY:

0.128

AC XY:

92653

AN XY:

725198

show subpopulations

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.0797

Gnomad4 ASJ exome

AF:

0.116

Gnomad4 EAS exome

AF:

0.116

Gnomad4 SAS exome

AF:

0.0674

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.122

AC:

18570

AN:

152208

Hom.:

1218

Cov.:

AF XY:

0.119

AC XY:

8883

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.0888

Gnomad4 ASJ

AF:

0.121

Gnomad4 EAS

AF:

0.117

Gnomad4 SAS

AF:

0.0667

Gnomad4 FIN

AF:

0.124

Gnomad4 NFE

AF:

0.138

Gnomad4 OTH

AF:

0.117

Alfa

AF:

0.128

Hom.:

645

Bravo

AF:

0.122

Asia WGS

AF:

0.0800

AC:

278

AN:

3478

EpiCase

AF:

0.135

EpiControl

AF:

0.129

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.19

dbscSNV1_RF

Benign

0.29

SpliceAI score (max)

0.090

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over