1-232026118-G-T

Position:

• chr1-232026118-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.2308-317G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 152,126 control chromosomes in the GnomAD database, including 52 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 0.017 (52 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293

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 = 0.0619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.2308-317G>T		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2974-317G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.2308-317G>T		intron_variant		5	NM_018662.3	A2
DISC1	ENST00000366637.8	c.2242-317G>T		intron_variant		5		P2
DISC1	ENST00000622252.4	c.*849-317G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 2595 AN: 152008 Hom.: 52 Cov.: 31

Gnomad AFR AF: 0.00401

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0245

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.0680

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.0122

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0173

Gnomad OTH AF: 0.0134

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

GnomAD4 genome AF: 0.0170 AC: 2590 AN: 152126 Hom.: 52 Cov.: 31 AF XY: 0.0173 AC XY: 1288 AN XY: 74380

Gnomad4 AFR AF: 0.00400

Gnomad4 AMR AF: 0.0244

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.0678

Gnomad4 SAS AF: 0.0542

Gnomad4 FIN AF: 0.0122

Gnomad4 NFE AF: 0.0173

Gnomad4 OTH AF: 0.0138

Alfa AF: 0.00913 Hom.: 2

Bravo AF: 0.0174

Asia WGS AF: 0.0570 AC: 202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16856254; hg19: chr1-232161864;