rs823165

chr1-231633700-T-Achr1-231633700-T-C

Variant summary

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

The NM_018662.3(DISC1):c.67+6766T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 151,984 control chromosomes in the GnomAD database, including 10,897 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 0.37 (10897 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.67+6766T>A		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.788+16794T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.67+6766T>A		intron_variant		5	NM_018662.3	A2

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55612 AN: 151866 Hom.: 10882 Cov.: 31

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.366 AC: 55662 AN: 151984 Hom.: 10897 Cov.: 31 AF XY: 0.371 AC XY: 27596 AN XY: 74292

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.364

Alfa AF: 0.345 Hom.: 1136

Bravo AF: 0.373

Asia WGS AF: 0.553 AC: 1923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	6.4
Dann	Benign	0.73

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: rs823165; hg19: chr1-231769446;