chr1-232041241-C-T

Position:

• chr1-232041241-C-T

Variant summary

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

The NM_018662.3(DISC1):​c.*4410C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,962 control chromosomes in the GnomAD database, including 6,712 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 (6712 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DISC1 NM_018662.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180

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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.*4410C>T		3_prime_UTR_variant	13/13	ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.7641C>T		non_coding_transcript_exon_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.*4410C>T		3_prime_UTR_variant	13/13	5	NM_018662.3	A2
DISC1	ENST00000622252.4	c.*5516C>T		3_prime_UTR_variant	12/12	5

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44647 AN: 151844 Hom.: 6711 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.295

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.294 AC: 44682 AN: 151962 Hom.: 6712 Cov.: 32 AF XY: 0.292 AC XY: 21699 AN XY: 74276

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.294

Alfa AF: 0.290 Hom.: 6414

Bravo AF: 0.296

Asia WGS AF: 0.320 AC: 1113 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.4
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16856322; hg19: chr1-232176987;