rs11122330

chr1-231762845-A-G

Variant summary

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

The NM_018662.3(DISC1):c.1269-4295A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,042 control chromosomes in the GnomAD database, including 1,571 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 0.14 (1571 hom., cov: 29)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270

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 (SAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1269-4295A>G		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.1990-4295A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1269-4295A>G		intron_variant		5	NM_018662.3	A2

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21456 AN: 151924 Hom.: 1571 Cov.: 29

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.0947

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.141 AC: 21479 AN: 152042 Hom.: 1571 Cov.: 29 AF XY: 0.143 AC XY: 10645 AN XY: 74308

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.0947

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.156

Alfa AF: 0.137 Hom.: 240

Bravo AF: 0.147

Asia WGS AF: 0.130 AC: 453 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	0.69
Dann	Benign	0.39

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: rs11122330; hg19: chr1-231898591;