rs1538979

Positions:

• chr1-231761122-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.1269-6018C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 151,974 control chromosomes in the GnomAD database, including 3,300 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 0.19 (3300 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1269-6018C>T		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.1990-6018C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1269-6018C>T		intron_variant		5	NM_018662.3	A2

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29499 AN: 151856 Hom.: 3293 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.204

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.194 AC: 29550 AN: 151974 Hom.: 3300 Cov.: 32 AF XY: 0.196 AC XY: 14587 AN XY: 74314

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.207

Alfa AF: 0.156 Hom.: 1894

Bravo AF: 0.205

Asia WGS AF: 0.219 AC: 759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.64
DANN	Benign	0.75

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: rs1538979; hg19: chr1-231896868;