1-231931311-T-G

Variant names:

• chr1-231931311-T-G
• rs821577
• NM_018662.3:c.1982-27517T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018662.3(DISC1):​c.1982-27517T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 152,008 control chromosomes in the GnomAD database, including 22,348 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 0.53 (22348 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 19 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]

DISC1-IT1 (HGNC:41325): (DISC1 intronic transcript 1)

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1982-27517T>G		intron_variant	Intron 9 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1982-27517T>G		intron_variant	Intron 9 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1982-27517T>G		intron_variant	Intron 9 of 12	5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80482 AN: 151890 Hom.: 22311 Cov.: 32

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.530 AC: 80562 AN: 152008 Hom.: 22348 Cov.: 32 AF XY: 0.533 AC XY: 39608 AN XY: 74300

African (AFR) AF: 0.674 AC: 27924 AN: 41454

American (AMR) AF: 0.515 AC: 7869 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1797 AN: 3468

East Asian (EAS) AF: 0.810 AC: 4183 AN: 5164

South Asian (SAS) AF: 0.521 AC: 2502 AN: 4806

European-Finnish (FIN) AF: 0.424 AC: 4481 AN: 10564

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30105 AN: 67956

Other (OTH) AF: 0.540 AC: 1140 AN: 2110

Alfa AF: 0.464 Hom.: 20514

Bravo AF: 0.543

Asia WGS AF: 0.676 AC: 2350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.55
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs821577; hg19: chr1-232067057; COSMIC: COSV64093642;