rs821618

Variant names:

• chr1-232009435-G-A
• rs821618
• ENST00000422590.6:n.*2554G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-232009435-G-A
• chr1-232009435-G-T

Variant summary

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

The ENST00000422590.6(DISC1):​n.*2554G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 575,828 control chromosomes in the GnomAD database, including 23,779 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 0.29 (6287 hom., cov: 31)
  • Exomes 𝑓: 0.28 (17492 hom.)
• Consequence: DISC1 ENST00000422590.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710
• Publications: 1 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.2307+386G>A		intron_variant	Intron 11 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.2307+386G>A		intron_variant	Intron 11 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.2241+452G>A		intron_variant	Intron 11 of 12	5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.289 AC: 42403 AN: 146728 Hom.: 6284 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.238

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.282 AC: 120891 AN: 429066 Hom.: 17492 Cov.: 6 AF XY: 0.283 AC XY: 57107 AN XY: 202126

African (AFR) AF: 0.339 AC: 2615 AN: 7716

American (AMR) AF: 0.155 AC: 158 AN: 1022

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 625 AN: 2724

East Asian (EAS) AF: 0.105 AC: 201 AN: 1918

South Asian (SAS) AF: 0.279 AC: 2358 AN: 8442

European-Finnish (FIN) AF: 0.356 AC: 69 AN: 194

Middle Eastern (MID) AF: 0.304 AC: 253 AN: 832

European-Non Finnish (NFE) AF: 0.283 AC: 110951 AN: 392360

Other (OTH) AF: 0.264 AC: 3661 AN: 13858

GnomAD4 genome AF: 0.289 AC: 42419 AN: 146762 Hom.: 6287 Cov.: 31 AF XY: 0.289 AC XY: 20619 AN XY: 71466

African (AFR) AF: 0.349 AC: 13467 AN: 38584

American (AMR) AF: 0.179 AC: 2653 AN: 14796

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3458

East Asian (EAS) AF: 0.123 AC: 614 AN: 4972

South Asian (SAS) AF: 0.279 AC: 1300 AN: 4666

European-Finnish (FIN) AF: 0.335 AC: 3215 AN: 9610

Middle Eastern (MID) AF: 0.228 AC: 63 AN: 276

European-Non Finnish (NFE) AF: 0.287 AC: 19334 AN: 67434

Other (OTH) AF: 0.255 AC: 526 AN: 2062

Alfa AF: 0.169 Hom.: 327

Bravo AF: 0.270

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.12
PhyloP100		-0.071
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: rs821618; hg19: chr1-232145181; COSMIC: COSV64093878; COSMIC: COSV64093878;