1-232030548-G-C

Variant names:

• chr1-232030548-G-C
• rs2806465
• NM_018662.3:c.2425+3996G>C

Variant summary

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

The NM_018662.3(DISC1):​c.2425+3996G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 151,942 control chromosomes in the GnomAD database, including 27,924 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 0.60 (27924 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195
• Publications: 4 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]

LOC124904549 (HGNC:):

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.2425+3996G>C		intron_variant	Intron 12 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.2425+3996G>C		intron_variant	Intron 12 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.2359+3996G>C		intron_variant	Intron 12 of 12	5		ENSP00000355597.6
DISC1	ENST00000622252.4	c.*966+3996G>C		intron_variant	Intron 11 of 11	5		ENSP00000481791.1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91072 AN: 151824 Hom.: 27875 Cov.: 32

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.600 AC: 91181 AN: 151942 Hom.: 27924 Cov.: 32 AF XY: 0.595 AC XY: 44159 AN XY: 74274

African (AFR) AF: 0.726 AC: 30095 AN: 41458

American (AMR) AF: 0.531 AC: 8109 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1882 AN: 3466

East Asian (EAS) AF: 0.430 AC: 2217 AN: 5154

South Asian (SAS) AF: 0.537 AC: 2579 AN: 4804

European-Finnish (FIN) AF: 0.517 AC: 5463 AN: 10566

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38783 AN: 67914

Other (OTH) AF: 0.608 AC: 1284 AN: 2112

Alfa AF: 0.436 Hom.: 1055

Bravo AF: 0.611

Asia WGS AF: 0.549 AC: 1908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.52
PhyloP100		-0.20
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: rs2806465; hg19: chr1-232166294;