rs821592

Positions:

• chr1-231958513-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.1982-315G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,084 control chromosomes in the GnomAD database, including 8,443 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 0.32 (8443 hom., cov: 33)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.564

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1982-315G>A		intron_variant		ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1982-315G>A		intron_variant		5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1982-315G>A		intron_variant		5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48538 AN: 151966 Hom.: 8427 Cov.: 33

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.319 AC: 48579 AN: 152084 Hom.: 8443 Cov.: 33 AF XY: 0.315 AC XY: 23411 AN XY: 74340

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.288

Alfa AF: 0.288 Hom.: 3789

Bravo AF: 0.318

Asia WGS AF: 0.256 AC: 893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.8
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs821592; hg19: chr1-232094259;