1-232037092-G-A

Position:

• chr1-232037092-G-A

Variant summary

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

The NM_018662.3(DISC1):​c.*261G>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 0.0379 in 277,472 control chromosomes in the GnomAD database, including 427 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 0.033 (152 hom., cov: 32)
  • Exomes 𝑓: 0.044 (275 hom.)
• Consequence: DISC1 NM_018662.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.*261G>A		3_prime_UTR_variant	13/13	ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.3492G>A		non_coding_transcript_exon_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.*261G>A		3_prime_UTR_variant	13/13	5	NM_018662.3	A2
DISC1	ENST00000366637.8	c.*261G>A		3_prime_UTR_variant	13/13	5		P2
DISC1	ENST00000622252.4	c.*1367G>A		3_prime_UTR_variant	12/12	5

Frequencies

GnomAD3 genomes AF: 0.0329 AC: 5002 AN: 152002 Hom.: 151 Cov.: 32

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0576

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.0382

Gnomad FIN AF: 0.0189

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0276

Gnomad OTH AF: 0.0432

GnomAD4 exome AF: 0.0439 AC: 5500 AN: 125352 Hom.: 275 Cov.: 3 AF XY: 0.0424 AC XY: 2691 AN XY: 63536

Gnomad4 AFR exome AF: 0.0192

Gnomad4 AMR exome AF: 0.0570

Gnomad4 ASJ exome AF: 0.0557

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.0338

Gnomad4 FIN exome AF: 0.0230

Gnomad4 NFE exome AF: 0.0281

Gnomad4 OTH exome AF: 0.0411

GnomAD4 genome AF: 0.0329 AC: 5010 AN: 152120 Hom.: 152 Cov.: 32 AF XY: 0.0331 AC XY: 2463 AN XY: 74358

Gnomad4 AFR AF: 0.0177

Gnomad4 AMR AF: 0.0576

Gnomad4 ASJ AF: 0.0513

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.0383

Gnomad4 FIN AF: 0.0189

Gnomad4 NFE AF: 0.0276

Gnomad4 OTH AF: 0.0433

Alfa AF: 0.0315 Hom.: 167

Bravo AF: 0.0355

Asia WGS AF: 0.0790 AC: 276 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	2.6
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3737597; hg19: chr1-232172838;