rs2295959

Positions:

• chr1-231818936-C-T

Variant summary

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

The ENST00000602281.5(DISC1):​c.*411C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0612 in 1,009,826 control chromosomes in the GnomAD database, including 2,685 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 0.094 (967 hom., cov: 32)
  • Exomes 𝑓: 0.055 (1718 hom.)
• Consequence: DISC1 ENST00000602281.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.487

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1981+419C>T		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2647+419C>T		intron_variant, non_coding_transcript_variant
LOC105373170	XR_949268.4	n.295+3789G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1981+419C>T		intron_variant		5	NM_018662.3	A2
	ENST00000651424.1	n.258+3789G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0937 AC: 14247 AN: 152108 Hom.: 963 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0427

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0527

Gnomad OTH AF: 0.0912

GnomAD4 exome AF: 0.0554 AC: 47533 AN: 857600 Hom.: 1718 Cov.: 33 AF XY: 0.0550 AC XY: 21852 AN XY: 397248

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.340

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.0277

Gnomad4 NFE exome AF: 0.0488

Gnomad4 OTH exome AF: 0.0801

GnomAD4 genome AF: 0.0937 AC: 14271 AN: 152226 Hom.: 967 Cov.: 32 AF XY: 0.0953 AC XY: 7091 AN XY: 74426

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.0427

Gnomad4 NFE AF: 0.0527

Gnomad4 OTH AF: 0.0936

Alfa AF: 0.0628 Hom.: 519

Bravo AF: 0.101

Asia WGS AF: 0.236 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.2
DANN	Benign	0.82

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: rs2295959; hg19: chr1-231954682;