rs967244

chr1-231812900-G-Achr1-231812900-G-Cchr1-231812900-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.1793-5429G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 152,166 control chromosomes in the GnomAD database, including 50,411 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 0.81 (50411 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

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]

LOC105373170 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1793-5429G>A		intron_variant		ENST00000439617.8
LOC105373170	XR_949268.4	n.1687C>T		non_coding_transcript_exon_variant	3/4
TSNAX-DISC1	NR_028393.1	n.2459-5429G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1793-5429G>A		intron_variant		5	NM_018662.3	A2
	ENST00000651424.1	n.258+9825C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123729 AN: 152046 Hom.: 50366 Cov.: 32

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.750

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.814 AC: 123833 AN: 152166 Hom.: 50411 Cov.: 32 AF XY: 0.814 AC XY: 60528 AN XY: 74400

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.822

Gnomad4 ASJ AF: 0.831

Gnomad4 EAS AF: 0.809

Gnomad4 SAS AF: 0.745

Gnomad4 FIN AF: 0.847

Gnomad4 NFE AF: 0.819

Gnomad4 OTH AF: 0.808

Alfa AF: 0.811 Hom.: 102022

Bravo AF: 0.811

Asia WGS AF: 0.786 AC: 2737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.7
Dann	Benign	0.28

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: rs967244; hg19: chr1-231948646;