rs821598

chr1-231967601-C-T

Variant summary

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

The NM_018662.3(DISC1):c.2042+8713C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,966 control chromosomes in the GnomAD database, including 8,977 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 0.33 (8977 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.2042+8713C>T		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2708+8713C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.2042+8713C>T		intron_variant		5	NM_018662.3	A2

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50532 AN: 151846 Hom.: 8965 Cov.: 32

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.333 AC: 50585 AN: 151966 Hom.: 8977 Cov.: 32 AF XY: 0.333 AC XY: 24729 AN XY: 74272

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.300

Alfa AF: 0.321 Hom.: 1549

Bravo AF: 0.321

Asia WGS AF: 0.320 AC: 1112 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.67
Dann	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs821598; hg19: chr1-232103347; COSMIC: COSV64093667;