rs3081

Variant names:

• chr1-231866586-C-G
• rs3081
• ENST00000366636.8:c.*8C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001012959.2(DISC1):​c.*8C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0505 in 1,370,204 control chromosomes in the GnomAD database, including 1,995 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.041 (158 hom., cov: 32)
  • Exomes 𝑓: 0.052 (1837 hom.)
• Consequence: DISC1 NM_001012959.2 3_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.296
• Publications: 17 publications found

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:49177): (TSNAX-DISC1 readthrough (NMD candidate)) This gene represents naturally occurring read-through transcription between the neighboring TSNAX (translin-associated factor X) and DISC1 (disrupted in schizophrenia 1) genes on chromosome 1. Alternative splicing results in multiple transcript variants, all of which are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to be protein-coding. These alterations in gene processing may be associated with risk for psychiatric illness, most notably, schizophrenia. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-231866586-C-G is Benign according to our data. Variant chr1-231866586-C-G is described in ClinVar as Benign. ClinVar VariationId is 3060171.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0609 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012959.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	NM_018662.3	MANE Select	c.1981+48069C>G		intron	N/A	NP_061132.2	Q9NRI5-1
	DISC1	NM_001012959.2		c.*8C>G		3_prime_UTR	Exon 10 of 10	NP_001012977.1	Q9NRI5-3
	DISC1	NM_001164537.2		c.2077+48069C>G		intron	N/A	NP_001158009.1	C4P096

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	ENST00000366636.8	TSL:1	c.*8C>G		3_prime_UTR	Exon 10 of 10	ENSP00000355596.4	Q9NRI5-3
	DISC1	ENST00000439617.8	TSL:5 MANE Select	c.1981+48069C>G		intron	N/A	ENSP00000403888.4	Q9NRI5-1
	DISC1	ENST00000366637.8	TSL:5	c.1981+48069C>G		intron	N/A	ENSP00000355597.6	Q9NRI5-2

Frequencies

GnomAD3 genomes AF: 0.0407 AC: 6194 AN: 152128 Hom.: 157 Cov.: 32

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0403

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0666

Gnomad SAS AF: 0.0636

Gnomad FIN AF: 0.0455

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0510

Gnomad OTH AF: 0.0506

GnomAD2 exomes AF: 0.0488 AC: 12126 AN: 248290 AF XY: 0.0521

Gnomad AFR exome AF: 0.0110

Gnomad AMR exome AF: 0.0267

Gnomad ASJ exome AF: 0.0900

Gnomad EAS exome AF: 0.0653

Gnomad FIN exome AF: 0.0378

Gnomad NFE exome AF: 0.0528

Gnomad OTH exome AF: 0.0559

GnomAD4 exome AF: 0.0518 AC: 63043 AN: 1217958 Hom.: 1837 Cov.: 18 AF XY: 0.0529 AC XY: 32713 AN XY: 618238

African (AFR) AF: 0.0106 AC: 309 AN: 29256

American (AMR) AF: 0.0273 AC: 1211 AN: 44412

Ashkenazi Jewish (ASJ) AF: 0.0940 AC: 2324 AN: 24722

East Asian (EAS) AF: 0.0560 AC: 2157 AN: 38514

South Asian (SAS) AF: 0.0621 AC: 5042 AN: 81210

European-Finnish (FIN) AF: 0.0351 AC: 1870 AN: 53324

Middle Eastern (MID) AF: 0.0723 AC: 384 AN: 5312

European-Non Finnish (NFE) AF: 0.0525 AC: 46708 AN: 888932

Other (OTH) AF: 0.0581 AC: 3038 AN: 52276

GnomAD4 genome AF: 0.0407 AC: 6197 AN: 152246 Hom.: 158 Cov.: 32 AF XY: 0.0407 AC XY: 3028 AN XY: 74420

African (AFR) AF: 0.0116 AC: 483 AN: 41542

American (AMR) AF: 0.0403 AC: 616 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 358 AN: 3472

East Asian (EAS) AF: 0.0667 AC: 345 AN: 5172

South Asian (SAS) AF: 0.0638 AC: 308 AN: 4826

European-Finnish (FIN) AF: 0.0455 AC: 482 AN: 10594

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0510 AC: 3471 AN: 68030

Other (OTH) AF: 0.0501 AC: 106 AN: 2116

Alfa AF: 0.0531 Hom.: 65

Bravo AF: 0.0382

Asia WGS AF: 0.0570 AC: 198 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DISC1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.53
PhyloP100		0.30
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3081; hg19: chr1-232002332; COSMIC: COSV64084735;