1-231670540-G-C

Position:

• chr1-231670540-G-C

Variant summary

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

The NM_018662.3(DISC1):​c.68-23286G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,034 control chromosomes in the GnomAD database, including 16,923 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 0.46 (16922 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.573

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISC1	NM_018662.3	c.68-23286G>C		intron_variant		ENST00000439617.8	NP_061132.2
TSNAX-DISC1	NR_028393.1	n.789-23286G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.68-23286G>C		intron_variant		5	NM_018662.3	ENSP00000403888	A2

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70302 AN: 151914 Hom.: 16884 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.450

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 FIN exome AF: 1.00

GnomAD4 genome AF: 0.463 AC: 70397 AN: 152032 Hom.: 16922 Cov.: 32 AF XY: 0.465 AC XY: 34518 AN XY: 74288

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.822

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.455

Alfa AF: 0.269 Hom.: 585

Bravo AF: 0.475

Asia WGS AF: 0.620 AC: 2157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.69
DANN	Benign	0.49

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: rs4366301; hg19: chr1-231806286;