1-232038427-T-C

Position:

• chr1-232038427-T-C

Variant summary

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

The NM_018662.3(DISC1):​c.*1596T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,910 control chromosomes in the GnomAD database, including 10,455 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 0.36 (10454 hom., cov: 31)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: DISC1 NM_018662.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISC1	NM_018662.3	c.*1596T>C		3_prime_UTR_variant	13/13	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.*1596T>C		3_prime_UTR_variant	13/13	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.*1596T>C		3_prime_UTR_variant	13/13	5		ENSP00000355597.6
DISC1	ENST00000622252.4	c.*2702T>C		3_prime_UTR_variant	12/12	5		ENSP00000481791.1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53903 AN: 151788 Hom.: 10442 Cov.: 31

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.344

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.355 AC: 53964 AN: 151906 Hom.: 10454 Cov.: 31 AF XY: 0.351 AC XY: 26050 AN XY: 74252

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.343

Alfa AF: 0.297 Hom.: 11664

Bravo AF: 0.367

Asia WGS AF: 0.337 AC: 1172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.039
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9729179; hg19: chr1-232174173;