1-231784475-G-A

Position:

• chr1-231784475-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.1635-10767G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 151,978 control chromosomes in the GnomAD database, including 8,324 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 0.30 (8324 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

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]

(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 (NFE) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1635-10767G>A		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2355+13405G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1635-10767G>A		intron_variant		5	NM_018662.3	A2
	ENST00000651424.1	n.317+2810C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45618 AN: 151858 Hom.: 8326 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.0272

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.300 AC: 45605 AN: 151978 Hom.: 8324 Cov.: 32 AF XY: 0.299 AC XY: 22209 AN XY: 74246

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.0272

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.303

Alfa AF: 0.367 Hom.: 6426

Bravo AF: 0.280

Asia WGS AF: 0.173 AC: 609 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	7.8
DANN	Benign	0.77

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: rs17817356; hg19: chr1-231920221;