rs843979

Variant names:

• chr1-231994862-C-G
• rs843979
• NM_018662.3:c.2043-13923C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-231994862-C-G
• chr1-231994862-C-T

Variant summary

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

The NM_018662.3(DISC1):​c.2043-13923C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,010 control chromosomes in the GnomAD database, including 16,084 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 0.43 (16084 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480
• Publications: 10 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 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.2043-13923C>G		intron	N/A	NP_061132.2	Q9NRI5-1
	DISC1	NM_001164537.2		c.2139-13923C>G		intron	N/A	NP_001158009.1	C4P096
	DISC1	NM_001012957.2		c.2043-13923C>G		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.2043-13923C>G		intron	N/A	ENSP00000403888.4	Q9NRI5-1
	DISC1	ENST00000366637.8	TSL:5	c.2043-13923C>G		intron	N/A	ENSP00000355597.6	Q9NRI5-2
	DISC1	ENST00000535983.5	TSL:1	c.1982-13923C>G		intron	N/A	ENSP00000443996.1	Q9NRI5-8

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65489 AN: 151892 Hom.: 16063 Cov.: 32

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.431 AC: 65554 AN: 152010 Hom.: 16084 Cov.: 32 AF XY: 0.430 AC XY: 31919 AN XY: 74304

African (AFR) AF: 0.682 AC: 28259 AN: 41434

American (AMR) AF: 0.293 AC: 4473 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1118 AN: 3466

East Asian (EAS) AF: 0.361 AC: 1865 AN: 5166

South Asian (SAS) AF: 0.425 AC: 2046 AN: 4812

European-Finnish (FIN) AF: 0.364 AC: 3841 AN: 10560

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22613 AN: 67970

Other (OTH) AF: 0.382 AC: 807 AN: 2112

Alfa AF: 0.205 Hom.: 389

Bravo AF: 0.433

Asia WGS AF: 0.421 AC: 1464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.34
PhyloP100		0.048
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: rs843979; hg19: chr1-232130608; COSMIC: COSV64093716;