1-231953994-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.1982-4834A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,134 control chromosomes in the GnomAD database, including 1,869 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 0.15 (1869 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1982-4834A>G		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2648-4834A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1982-4834A>G		intron_variant		5	NM_018662.3	A2

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22503 AN: 152016 Hom.: 1866 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.148 AC: 22531 AN: 152134 Hom.: 1869 Cov.: 32 AF XY: 0.152 AC XY: 11269 AN XY: 74368

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.144

Alfa AF: 0.132 Hom.: 427

Bravo AF: 0.152

Asia WGS AF: 0.272 AC: 943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.4
Dann	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9431736; hg19: chr1-232089740;