rs2038636

Positions:

• chr1-231919503-G-A

Variant summary

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

The NM_018662.3(DISC1):​c.1982-39325G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,006 control chromosomes in the GnomAD database, including 21,129 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 0.52 (21129 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1982-39325G>A		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2648-39325G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1982-39325G>A		intron_variant		5	NM_018662.3	A2

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78611 AN: 151888 Hom.: 21128 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.517 AC: 78626 AN: 152006 Hom.: 21129 Cov.: 32 AF XY: 0.513 AC XY: 38100 AN XY: 74288

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.506

Alfa AF: 0.562 Hom.: 17826

Bravo AF: 0.507

Asia WGS AF: 0.321 AC: 1117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2038636; hg19: chr1-232055249;