1-231800404-T-C

Position:

• chr1-231800404-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.1792+194T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,044 control chromosomes in the GnomAD database, including 42,255 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 0.74 (42255 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1792+194T>C		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2458+194T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1792+194T>C		intron_variant		5	NM_018662.3	A2
	ENST00000651424.1	n.259-13061A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.744 AC: 113022 AN: 151926 Hom.: 42246 Cov.: 32

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.744 AC: 113079 AN: 152044 Hom.: 42255 Cov.: 32 AF XY: 0.746 AC XY: 55481 AN XY: 74322

Gnomad4 AFR AF: 0.714

Gnomad4 AMR AF: 0.783

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.608

Gnomad4 SAS AF: 0.759

Gnomad4 FIN AF: 0.771

Gnomad4 NFE AF: 0.761

Gnomad4 OTH AF: 0.750

Alfa AF: 0.759 Hom.: 56322

Bravo AF: 0.741

Asia WGS AF: 0.682 AC: 2373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.53
DANN	Benign	0.46

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: rs2255340; hg19: chr1-231936150; COSMIC: COSV54414883;