rs2793101

Positions:

• chr1-231768532-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.1398+1263C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0977 in 150,392 control chromosomes in the GnomAD database, including 761 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 0.098 (761 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316

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 (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1398+1263C>T		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2119+1263C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1398+1263C>T		intron_variant		5	NM_018662.3	A2
	ENST00000651424.1	n.537-170G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0977 AC: 14675 AN: 150274 Hom.: 761 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0554

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0247

Gnomad SAS AF: 0.0705

Gnomad FIN AF: 0.0807

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.0977 AC: 14689 AN: 150392 Hom.: 761 Cov.: 32 AF XY: 0.0929 AC XY: 6816 AN XY: 73388

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0554

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0251

Gnomad4 SAS AF: 0.0710

Gnomad4 FIN AF: 0.0807

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.105

Alfa AF: 0.113 Hom.: 115

Bravo AF: 0.0947

Asia WGS AF: 0.0480 AC: 169 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	5.9
DANN	Benign	0.63

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: rs2793101; hg19: chr1-231904278;