rs821723

Positions:

• chr1-231899450-G-A
• chr1-231899450-G-C
• chr1-231899450-G-T

Variant summary

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

The NM_018662.3(DISC1):​c.1982-59378G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 152,212 control chromosomes in the GnomAD database, including 63,300 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 0.91 (63300 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

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]

DISC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1982-59378G>A		intron_variant		ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1982-59378G>A		intron_variant		5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1982-59378G>A		intron_variant		5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.911 AC: 138586 AN: 152092 Hom.: 63254 Cov.: 31

Gnomad AFR AF: 0.953

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.932

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.871

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.915

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

GnomAD4 genome AF: 0.911 AC: 138691 AN: 152212 Hom.: 63300 Cov.: 31 AF XY: 0.911 AC XY: 67807 AN XY: 74396

Gnomad4 AFR AF: 0.953

Gnomad4 AMR AF: 0.932

Gnomad4 ASJ AF: 0.890

Gnomad4 EAS AF: 0.990

Gnomad4 SAS AF: 0.919

Gnomad4 FIN AF: 0.871

Gnomad4 NFE AF: 0.883

Gnomad4 OTH AF: 0.912

Alfa AF: 0.901 Hom.: 8812

Bravo AF: 0.915

Asia WGS AF: 0.928 AC: 3225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs821723; hg19: chr1-232035196;