rs823161

chr1-231639271-G-Achr1-231639271-G-Cchr1-231639271-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018662.3(DISC1):c.67+12337G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,934 control chromosomes in the GnomAD database, including 11,655 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 0.38 (11655 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.96

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]

TSNAX-DISC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.67+12337G>A		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.788+22365G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.67+12337G>A		intron_variant		5	NM_018662.3	A2

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57803 AN: 151816 Hom.: 11636 Cov.: 31

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.381 AC: 57858 AN: 151934 Hom.: 11655 Cov.: 31 AF XY: 0.385 AC XY: 28614 AN XY: 74230

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.379

Alfa AF: 0.331 Hom.: 4498

Bravo AF: 0.389

Asia WGS AF: 0.558 AC: 1943 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	0.0050
Dann	Benign	0.70

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

Other links and lift over

dbSNP: rs823161; hg19: chr1-231775017;