rs1340982

Positions:

• chr1-231726286-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.1118-23640G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,116 control chromosomes in the GnomAD database, including 11,732 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 0.39 (11732 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1118-23640G>A		intron_variant		ENST00000439617.8	NP_061132.2
TSNAX-DISC1	NR_028393.1	n.1839-23640G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1118-23640G>A		intron_variant		5	NM_018662.3	ENSP00000403888	A2

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58594 AN: 151998 Hom.: 11711 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.386 AC: 58658 AN: 152116 Hom.: 11732 Cov.: 32 AF XY: 0.379 AC XY: 28203 AN XY: 74344

Gnomad4 AFR AF: 0.493

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.409

Alfa AF: 0.363 Hom.: 1290

Bravo AF: 0.398

Asia WGS AF: 0.366 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.43
DANN	Benign	0.35

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: rs1340982; hg19: chr1-231862032;