1-231776230-C-T

Position:

• chr1-231776230-C-T

Variant summary

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

The NM_018662.3(DISC1):​c.1634+5160C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 151,960 control chromosomes in the GnomAD database, including 6,114 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 0.27 (6114 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1634+5160C>T		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2355+5160C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1634+5160C>T		intron_variant		5	NM_018662.3	A2
	ENST00000651424.1	n.318-1467G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41651 AN: 151842 Hom.: 6117 Cov.: 31

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.274 AC: 41666 AN: 151960 Hom.: 6114 Cov.: 31 AF XY: 0.277 AC XY: 20558 AN XY: 74278

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.318

Alfa AF: 0.286 Hom.: 9403

Bravo AF: 0.284

Asia WGS AF: 0.417 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.42
DANN	Benign	0.70

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: rs2812391; hg19: chr1-231911976;