1-231715533-T-C

Variant names:

• chr1-231715533-T-C
• rs1934909
• NM_018662.3:c.1117+13509T>C

Variant summary

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

The NM_001164537.2(DISC1):​c.1117+13509T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 152,246 control chromosomes in the GnomAD database, including 59,814 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 0.89 (59814 hom., cov: 31)
• Consequence: DISC1 NM_001164537.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164537.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	NM_018662.3	MANE Select	c.1117+13509T>C		intron	N/A	NP_061132.2
	DISC1	NM_001164537.2		c.1117+13509T>C		intron	N/A	NP_001158009.1
	DISC1	NM_001012957.2		c.1117+13509T>C		intron	N/A	NP_001012975.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	ENST00000439617.8	TSL:5 MANE Select	c.1117+13509T>C		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.1117+13509T>C		intron	N/A	ENSP00000355597.6
	DISC1	ENST00000366633.7	TSL:1	c.1117+13509T>C		intron	N/A	ENSP00000355593.3

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134710 AN: 152128 Hom.: 59766 Cov.: 31

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.920

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.881

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.897

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

GnomAD4 genome AF: 0.886 AC: 134814 AN: 152246 Hom.: 59814 Cov.: 31 AF XY: 0.888 AC XY: 66121 AN XY: 74426

African (AFR) AF: 0.918 AC: 38119 AN: 41538

American (AMR) AF: 0.920 AC: 14070 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3046 AN: 3472

East Asian (EAS) AF: 0.983 AC: 5086 AN: 5176

South Asian (SAS) AF: 0.881 AC: 4248 AN: 4824

European-Finnish (FIN) AF: 0.892 AC: 9458 AN: 10600

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.851 AC: 57878 AN: 68018

Other (OTH) AF: 0.895 AC: 1893 AN: 2114

Alfa AF: 0.863 Hom.: 97172

Bravo AF: 0.890

Asia WGS AF: 0.912 AC: 3172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.53
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1934909; hg19: chr1-231851279;