rs2812385

chr1-231728256-G-T

Variant summary

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

The NM_018662.3(DISC1):c.1118-21670G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,024 control chromosomes in the GnomAD database, including 26,327 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 0.58 (26327 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.793

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1118-21670G>T		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.1839-21670G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1118-21670G>T		intron_variant		5	NM_018662.3	A2

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88471 AN: 151906 Hom.: 26318 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.582 AC: 88502 AN: 152024 Hom.: 26327 Cov.: 32 AF XY: 0.583 AC XY: 43303 AN XY: 74316

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.585

Alfa AF: 0.639 Hom.: 36963

Bravo AF: 0.574

Asia WGS AF: 0.578 AC: 2007 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.6
Dann	Benign	0.52

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: rs2812385; hg19: chr1-231864002;