rs4658971

Variant names:

• chr1-231972068-C-T
• rs4658971
• NM_018662.3:c.2042+13180C>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.2042+13180C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 151,984 control chromosomes in the GnomAD database, including 3,531 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 0.15 (3531 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.452
• Publications: 9 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 = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.2042+13180C>T		intron_variant	Intron 10 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.2042+13180C>T		intron_variant	Intron 10 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.2042+13180C>T		intron_variant	Intron 10 of 12	5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23094 AN: 151866 Hom.: 3525 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0767

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.0642

Gnomad FIN AF: 0.0324

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0451

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.152 AC: 23123 AN: 151984 Hom.: 3531 Cov.: 32 AF XY: 0.150 AC XY: 11143 AN XY: 74292

African (AFR) AF: 0.386 AC: 16010 AN: 41454

American (AMR) AF: 0.116 AC: 1763 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0767 AC: 265 AN: 3456

East Asian (EAS) AF: 0.203 AC: 1053 AN: 5178

South Asian (SAS) AF: 0.0630 AC: 303 AN: 4812

European-Finnish (FIN) AF: 0.0324 AC: 343 AN: 10584

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0451 AC: 3065 AN: 67922

Other (OTH) AF: 0.127 AC: 267 AN: 2110

Alfa AF: 0.0785 Hom.: 4597

Bravo AF: 0.172

Asia WGS AF: 0.135 AC: 469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.56
DANN	Benign	0.65
PhyloP100		-0.45
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: rs4658971; hg19: chr1-232107814;