1-231882067-G-A

Position:

• chr1-231882067-G-A

Variant summary

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

The NM_018662.3(DISC1):​c.1981+63550G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,100 control chromosomes in the GnomAD database, including 7,015 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 0.30 (7015 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1981+63550G>A		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2647+63550G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1981+63550G>A		intron_variant		5	NM_018662.3	A2

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45511 AN: 151982 Hom.: 7014 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.299 AC: 45516 AN: 152100 Hom.: 7015 Cov.: 32 AF XY: 0.299 AC XY: 22225 AN XY: 74346

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.301

Alfa AF: 0.260 Hom.: 1115

Bravo AF: 0.294

Asia WGS AF: 0.210 AC: 729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.85
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11122359; hg19: chr1-232017813; COSMIC: COSV64092174;