1-232039029-T-C

Position:

• chr1-232039029-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.*2198T>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 0.358 in 152,138 control chromosomes in the GnomAD database, including 10,705 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 (10705 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DISC1 NM_018662.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

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 = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISC1	NM_018662.3	c.*2198T>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.*2198T>C		3_prime_UTR_variant	13/13	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.*2198T>C		3_prime_UTR_variant	13/13	5		ENSP00000355597.6
DISC1	ENST00000622252.4	c.*3304T>C		3_prime_UTR_variant	12/12	5		ENSP00000481791.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54431 AN: 152020 Hom.: 10693 Cov.: 32

Gnomad AFR AF: 0.521

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: 0.296

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.345

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: 0.358 AC: 54492 AN: 152138 Hom.: 10705 Cov.: 32 AF XY: 0.354 AC XY: 26291 AN XY: 74366

Gnomad4 AFR AF: 0.521

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: 0.344

Alfa AF: 0.307 Hom.: 9351

Bravo AF: 0.370

Asia WGS AF: 0.337 AC: 1173 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	0.28
DANN	Benign	0.25

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1411771; hg19: chr1-232174775;