1-232011348-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.2307+2299T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,998 control chromosomes in the GnomAD database, including 20,871 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 0.48 (20871 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774

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 = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.2307+2299T>C		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2973+2299T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.2307+2299T>C		intron_variant		5	NM_018662.3	A2
DISC1	ENST00000366637.8	c.2241+2365T>C		intron_variant		5		P2
DISC1	ENST00000622252.4	c.*848+2299T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73573 AN: 151880 Hom.: 20831 Cov.: 31

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.485 AC: 73655 AN: 151998 Hom.: 20871 Cov.: 31 AF XY: 0.483 AC XY: 35892 AN XY: 74292

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.426

Alfa AF: 0.424 Hom.: 1954

Bravo AF: 0.492

Asia WGS AF: 0.484 AC: 1682 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	2.1
Dann	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs821624; hg19: chr1-232147094; COSMIC: COSV64093896; COSMIC: COSV64093896;