1-231877447-T-C

Variant names:

• chr1-231877447-T-C
• rs11122355
• NM_018662.3:c.1981+58930T>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.1981+58930T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 152,304 control chromosomes in the GnomAD database, including 61,317 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 0.90 (61317 hom., cov: 33)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.985
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018662.3. 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+58930T>C		intron	N/A	NP_061132.2	Q9NRI5-1
	DISC1	NM_001164537.2		c.2077+58930T>C		intron	N/A	NP_001158009.1	C4P096
	DISC1	NM_001012957.2		c.1981+58930T>C		intron	N/A	NP_001012975.1	Q9NRI5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	ENST00000439617.8	TSL:5 MANE Select	c.1981+58930T>C		intron	N/A	ENSP00000403888.4	Q9NRI5-1
	DISC1	ENST00000366637.8	TSL:5	c.1981+58930T>C		intron	N/A	ENSP00000355597.6	Q9NRI5-2
	DISC1	ENST00000535983.5	TSL:1	c.1981+58930T>C		intron	N/A	ENSP00000443996.1	Q9NRI5-8

Frequencies

GnomAD3 genomes AF: 0.897 AC: 136454 AN: 152186 Hom.: 61262 Cov.: 33

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.926

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.871

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.899

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

GnomAD4 genome AF: 0.897 AC: 136568 AN: 152304 Hom.: 61317 Cov.: 33 AF XY: 0.899 AC XY: 66923 AN XY: 74478

African (AFR) AF: 0.903 AC: 37534 AN: 41558

American (AMR) AF: 0.926 AC: 14167 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 3104 AN: 3470

East Asian (EAS) AF: 0.996 AC: 5167 AN: 5188

South Asian (SAS) AF: 0.933 AC: 4509 AN: 4832

European-Finnish (FIN) AF: 0.871 AC: 9240 AN: 10614

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.881 AC: 59945 AN: 68020

Other (OTH) AF: 0.900 AC: 1902 AN: 2114

Alfa AF: 0.891 Hom.: 20669

Bravo AF: 0.899

Asia WGS AF: 0.958 AC: 3329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.91
DANN	Benign	0.73
PhyloP100		-0.98
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: rs11122355; hg19: chr1-232013193;