rs4658945

Variant names:

• chr1-231783095-C-A
• rs4658945
• NM_018662.3:c.1634+12025C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-231783095-C-A
• chr1-231783095-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.1634+12025C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,006 control chromosomes in the GnomAD database, including 986 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 0.10 (986 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511
• Publications: 7 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]

ENSG00000286071 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1634+12025C>A		intron_variant	Intron 6 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1634+12025C>A		intron_variant	Intron 6 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1634+12025C>A		intron_variant	Intron 6 of 12	5		ENSP00000355597.6
TSNAX-DISC1	ENST00000602956.5	n.*1495+12025C>A		intron_variant	Intron 10 of 12	2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15608 AN: 151890 Hom.: 985 Cov.: 31

Gnomad AFR AF: 0.0402

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.0805

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0753

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.103 AC: 15613 AN: 152006 Hom.: 986 Cov.: 31 AF XY: 0.101 AC XY: 7476 AN XY: 74286

African (AFR) AF: 0.0402 AC: 1666 AN: 41458

American (AMR) AF: 0.0806 AC: 1231 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 445 AN: 3470

East Asian (EAS) AF: 0.108 AC: 558 AN: 5164

South Asian (SAS) AF: 0.0746 AC: 359 AN: 4814

European-Finnish (FIN) AF: 0.127 AC: 1342 AN: 10540

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9506 AN: 67972

Other (OTH) AF: 0.103 AC: 219 AN: 2116

Alfa AF: 0.00226 Hom.: 62128

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.28
DANN	Benign	0.66
PhyloP100		-0.51
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: rs4658945; hg19: chr1-231918841;