rs11122324

Variant names:

• chr1-231723435-G-A
• rs11122324
• ENST00000317586.8:c.*834G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-231723435-G-A
• chr1-231723435-G-C
• chr1-231723435-G-T

Variant summary

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

The NM_001164550.2(DISC1):​c.*850G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 985,294 control chromosomes in the GnomAD database, including 62,125 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 0.36 (10182 hom., cov: 32)
  • Exomes 𝑓: 0.35 (51943 hom.)
• Consequence: DISC1 NM_001164550.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197
• Publications: 16 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164550.2. 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.1117+21411G>A		intron	N/A	NP_061132.2
	DISC1	NM_001164550.2		c.*850G>A		3_prime_UTR	Exon 5 of 5	NP_001158022.1
	DISC1	NM_001164552.2		c.*927G>A		3_prime_UTR	Exon 5 of 5	NP_001158024.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	ENST00000317586.8	TSL:1	c.*834G>A		3_prime_UTR	Exon 3 of 3	ENSP00000320784.4
	DISC1	ENST00000439617.8	TSL:5 MANE Select	c.1117+21411G>A		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.1117+21411G>A		intron	N/A	ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55231 AN: 151922 Hom.: 10168 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.390

GnomAD4 exome AF: 0.353 AC: 293786 AN: 833252 Hom.: 51943 Cov.: 31 AF XY: 0.352 AC XY: 135580 AN XY: 384796

African (AFR) AF: 0.432 AC: 6812 AN: 15786

American (AMR) AF: 0.361 AC: 359 AN: 994

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1708 AN: 5152

East Asian (EAS) AF: 0.354 AC: 1285 AN: 3632

South Asian (SAS) AF: 0.309 AC: 5078 AN: 16460

European-Finnish (FIN) AF: 0.320 AC: 89 AN: 278

Middle Eastern (MID) AF: 0.336 AC: 545 AN: 1620

European-Non Finnish (NFE) AF: 0.352 AC: 268247 AN: 762026

Other (OTH) AF: 0.354 AC: 9663 AN: 27304

GnomAD4 genome AF: 0.364 AC: 55282 AN: 152042 Hom.: 10182 Cov.: 32 AF XY: 0.357 AC XY: 26554 AN XY: 74316

African (AFR) AF: 0.419 AC: 17356 AN: 41430

American (AMR) AF: 0.353 AC: 5401 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1115 AN: 3470

East Asian (EAS) AF: 0.372 AC: 1924 AN: 5166

South Asian (SAS) AF: 0.292 AC: 1407 AN: 4820

European-Finnish (FIN) AF: 0.317 AC: 3345 AN: 10564

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23582 AN: 67984

Other (OTH) AF: 0.394 AC: 832 AN: 2112

Alfa AF: 0.346 Hom.: 13380

Bravo AF: 0.373

Asia WGS AF: 0.355 AC: 1237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.64
DANN	Benign	0.74
PhyloP100		-0.20
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: rs11122324; hg19: chr1-231859181; COSMIC: COSV107325754;