rs10864698

Positions:

• chr1-231882143-G-A

Variant summary

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

The NM_018662.3(DISC1):​c.1981+63626G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,172 control chromosomes in the GnomAD database, including 1,143 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 0.11 (1143 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1981+63626G>A		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2647+63626G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1981+63626G>A		intron_variant		5	NM_018662.3	A2

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17054 AN: 152054 Hom.: 1142 Cov.: 32

Gnomad AFR AF: 0.0806

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0835

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0738

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.112 AC: 17066 AN: 152172 Hom.: 1143 Cov.: 32 AF XY: 0.113 AC XY: 8371 AN XY: 74394

Gnomad4 AFR AF: 0.0805

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.0835

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.0738

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.120

Alfa AF: 0.116 Hom.: 403

Bravo AF: 0.118

Asia WGS AF: 0.234 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.2
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10864698; hg19: chr1-232017889;