1-231818863-G-A

Position:

• chr1-231818863-G-A

Variant summary

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

The ENST00000602281.5(DISC1):​c.*338G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,093,810 control chromosomes in the GnomAD database, including 31,362 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 0.23 (4390 hom., cov: 33)
  • Exomes 𝑓: 0.24 (26972 hom.)
• Consequence: DISC1 ENST00000602281.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1981+346G>A		intron_variant		ENST00000439617.8	NP_061132.2
TSNAX-DISC1	NR_028393.1	n.2647+346G>A		intron_variant, non_coding_transcript_variant
LOC105373170	XR_949268.4	n.295+3862C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1981+346G>A		intron_variant		5	NM_018662.3	ENSP00000403888	A2
	ENST00000651424.1	n.258+3862C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35499 AN: 151964 Hom.: 4378 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.238 AC: 223703 AN: 941728 Hom.: 26972 Cov.: 36 AF XY: 0.239 AC XY: 105293 AN XY: 441394

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.252

Gnomad4 ASJ exome AF: 0.230

Gnomad4 EAS exome AF: 0.402

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.316

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.237

GnomAD4 genome AF: 0.234 AC: 35527 AN: 152082 Hom.: 4390 Cov.: 33 AF XY: 0.238 AC XY: 17707 AN XY: 74330

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.214

Alfa AF: 0.235 Hom.: 7175

Bravo AF: 0.221

Asia WGS AF: 0.315 AC: 1098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.7
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs1535529; hg19: chr1-231954609;