rs11122330

Variant names:

• chr1-231762845-A-G
• rs11122330
• NM_018662.3:c.1269-4295A>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.1269-4295A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,042 control chromosomes in the GnomAD database, including 1,571 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 0.14 (1571 hom., cov: 29)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270
• 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]

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 (SAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1269-4295A>G		intron_variant	Intron 4 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1269-4295A>G		intron_variant	Intron 4 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1269-4295A>G		intron_variant	Intron 4 of 12	5		ENSP00000355597.6
TSNAX-DISC1	ENST00000602956.5	n.*1130-4295A>G		intron_variant	Intron 8 of 12	2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21456 AN: 151924 Hom.: 1571 Cov.: 29

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.0947

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.141 AC: 21479 AN: 152042 Hom.: 1571 Cov.: 29 AF XY: 0.143 AC XY: 10645 AN XY: 74308

African (AFR) AF: 0.159 AC: 6599 AN: 41444

American (AMR) AF: 0.153 AC: 2346 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 442 AN: 3470

East Asian (EAS) AF: 0.117 AC: 605 AN: 5178

South Asian (SAS) AF: 0.193 AC: 927 AN: 4812

European-Finnish (FIN) AF: 0.0947 AC: 1001 AN: 10566

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9109 AN: 67968

Other (OTH) AF: 0.156 AC: 330 AN: 2116

Alfa AF: 0.137 Hom.: 240

Bravo AF: 0.147

Asia WGS AF: 0.130 AC: 453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.69
DANN	Benign	0.39
PhyloP100		-0.27
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: rs11122330; hg19: chr1-231898591;