rs821722

Positions:

• chr1-231900284-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.1982-58544G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,030 control chromosomes in the GnomAD database, including 15,276 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 0.43 (15276 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.292

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1982-58544G>A		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2648-58544G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1982-58544G>A		intron_variant		5	NM_018662.3	A2

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66052 AN: 151912 Hom.: 15251 Cov.: 32

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.435 AC: 66119 AN: 152030 Hom.: 15276 Cov.: 32 AF XY: 0.434 AC XY: 32257 AN XY: 74302

Gnomad4 AFR AF: 0.520

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.757

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.460

Alfa AF: 0.397 Hom.: 12260

Bravo AF: 0.459

Asia WGS AF: 0.558 AC: 1937 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs821722; hg19: chr1-232036030;