1-232009141-A-G

Position:

• chr1-232009141-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000535983.5(DISC1):​c.*250A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,575,808 control chromosomes in the GnomAD database, including 62,744 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 (6466 hom., cov: 31)
  • Exomes 𝑓: 0.28 (56278 hom.)
• Consequence: DISC1 ENST00000535983.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISC1	NM_018662.3	c.2307+92A>G		intron_variant		ENST00000439617.8	NP_061132.2
TSNAX-DISC1	NR_028393.1	n.2973+92A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.2307+92A>G		intron_variant		5	NM_018662.3	ENSP00000403888	A2

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43312 AN: 151778 Hom.: 6460 Cov.: 31

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.252

GnomAD3 exomes AF: 0.259 AC: 52882 AN: 204542 Hom.: 7343 AF XY: 0.263 AC XY: 28794 AN XY: 109522

Gnomad AFR exome AF: 0.348

Gnomad AMR exome AF: 0.124

Gnomad ASJ exome AF: 0.244

Gnomad EAS exome AF: 0.116

Gnomad SAS exome AF: 0.276

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.293

Gnomad OTH exome AF: 0.262

GnomAD4 exome AF: 0.277 AC: 394268 AN: 1423912 Hom.: 56278 Cov.: 31 AF XY: 0.278 AC XY: 195492 AN XY: 703868

Gnomad4 AFR exome AF: 0.341

Gnomad4 AMR exome AF: 0.129

Gnomad4 ASJ exome AF: 0.236

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.274

Gnomad4 FIN exome AF: 0.322

Gnomad4 NFE exome AF: 0.286

Gnomad4 OTH exome AF: 0.266

GnomAD4 genome AF: 0.285 AC: 43346 AN: 151896 Hom.: 6466 Cov.: 31 AF XY: 0.284 AC XY: 21106 AN XY: 74206

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.256

Alfa AF: 0.274 Hom.: 5063

Bravo AF: 0.272

Asia WGS AF: 0.216 AC: 752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.6
DANN	Benign	0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs821617; hg19: chr1-232144887; COSMIC: COSV64110667; COSMIC: COSV64110667;